The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index; 1 of the 69 sources its claims cite were checked for support.
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease
Open accessAbstract
Glia have been implicated in Alzheimer’s disease (AD) pathogenesis. Variants of the microglia receptor triggering receptor expressed on myeloid cells 2 (TREM2) increase AD risk, and activation of disease-associated microglia (DAM) is dependent on TREM2 in mouse models of AD. We surveyed gene-expression changes associated with AD pathology and TREM2 in 5XFAD mice and in human AD by single-nucleus RNA sequencing. We confirmed the presence of Trem2-dependent DAM and identified a previously undiscovered Serpina3n+C4b+ reactive oligodendrocyte population in mice. Interestingly, remarkably different glial phenotypes were evident in human AD. Microglia signature was reminiscent of IRF8-driven reactive microglia in peripheral-nerve injury. Oligodendrocyte signatures suggested impaired axonal myelination and metabolic adaptation to neuronal degeneration. Astrocyte profiles indicated weakened metabolic coordination with neurons. Notably, the reactive phenotype of microglia was less evident in TREM2-R47H and TREM2-R62H carriers than in non-carriers, demonstrating a TREM2 requirement in both mouse and human AD, despite the marked species-specific differences. Single-nucleus RNA sequencing in a mouse model of Aβ accumulation and postmortem brain tissue from people with Alzheimer’s disease reveals substantial species-specific differences in transcriptional signatures, but both point to the contribution of glia and the importance of TREM2.
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128 Own result · 37 Not checked yet · 29 Own interpretation · 21 Own method · 2 No basis given · 1 Supported
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In the paper
“Collectively, these genes have been implicated in the coordination of lipid and oxidative metabolism between neurons and astrocytes30.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > The astrocyte signature indicates increase in glial scaring and loss of metabolic coordination between neurons and astrocytes
What the sources say
- Supportedcites [30] Ioannou, M. S. et al. Neuron–astrocyte metabolic coupling protects against activity-induced fatty acid toxicity. Cell 177, 1522–1535.e14 (2019). source
The section on astrocyte ROS-neutralizing machinery (p. 11) identifies genes involved in fatty-acid transport and metabolism and in neutralizing oxidative species, and links their expression to neurons’ reliance on astrocytes. The Introduction (p. 3) describes this as part of neuron–astrocyte metabolic coupling. (LLM, conf=0.89)
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In the paper
“Notably, the microglia cluster was much larger in the 5XFAD cortex than in the Trem2−/− 5XFAD and non-5XFAD cortices”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals a Trem2-dependent microgliosis at early stages of Aβ accumulation
plaincorrelationaln = 3- Asserted: passes — The authors put it forward as true.
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In the paper
“We confirmed the presence of Trem2-dependent DAM”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
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In the paper
“the reactive phenotype of microglia was less palpable in TREM2 R47H and R62H carriers than in non-carriers”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
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In the paper
“the Trem2−/− 5XFAD cortex contained a neuronal cluster with significantly fewer UMIs but relatively high expression of peptidylglycine alpha-amidating monooxygenase (Pam)”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals a Trem2-dependent microgliosis at early stages of Aβ accumulation
plaincorrelationaln = 3- Asserted: passes — The authors put it forward as true.
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In the paper
“the difference between microglial clusters in 5XFAD and Trem2−/− 5XFAD cortices was minimal at this stage”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals a Trem2-dependent microgliosis at early stages of Aβ accumulation
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In the paper
“identified a novel Serpina3n+C4b+ reactive oligodendrocyte population in mice.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
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In the paper
“Co-staining for either Serpina3n or C4b along with nuclear Olig2 showed perinuclear expression of Serpina3n and C4b in oligodendrocyte lineage cells of 5XFAD and Trem2−/− 5XFAD brains”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
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In the paper
“Volcano plot of 5XFAD vs WT oligodendrocytes in 7-month-old mice revealed a significant upregulation of three genes in particular – the complement component C4b, the serine protease inhibitor Serpina3n, and MHC-I (H2-D1) – in 5XFAD brains”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“5XFAD brains contained more Olig2+ nuclei indicative of oligodendrocyte lineage cells than did non-5XFAD brains”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Oligodendrocytes harbored the most strikingly upregulated genes.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“IPA pathway analysis of the most upregulated phosphopeptides identified synaptic signaling pathways as the most significantly upregulated in CV-5XFAD mice compared to CV mice”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Bulk proteomic analysis validates Trem2-dependent and -independent activation genes at the protein level
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“IF and immunohistochemistry (IHC) analyses corroborated increased expression of IRF8 in AD versus control samples, together with other markers indicative of microglial responses to Aβ, such as Iba1, CD68, and HLA-DR”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“sub-cluster Micro0 was highly enriched for expression of AD reactive genes”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“We identified oligodendrocyte (Oli0 and Oli1), excitatory neuron (Ex0 and Ex1), inhibitory neuron (In), astrocyte (Astro), microglia (Micro), OPCs and endothelial cell (Endo) clusters”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Non-neuronal populations, including microglia, astrocytes and oligodendrocytes, evinced more substantial changes.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, no enrichment of oligodendrocytes adjacent to plaques was observed”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we identified scores of additional genes that are moderately upregulated in the 5XFAD model in various cell types (Extended Data Fig. 5a–g) independently of TREM2”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Transcriptional changes in neuronal and other non-neuronal populations in response to Aβ are minimal
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In the paper
“an oligodendrocyte cell line upregulated C4 when exposed to Aβ, as well as alpha-2-macroglobulin and cytokines known to be released by microglia”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Egr1, a transcriptional regulator that mediates cell survival and proliferation, was substantially downregulated in excitatory neuron clusters”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Transcriptional changes in neuronal and other non-neuronal populations in response to Aβ are minimal
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“AD microglia expressed fewer transcripts of genes involved in iron and divalent metal ion transport (SLC25A37) and storage (HAMP, FTH1)”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“the neuronal clusters, especially that enriched for neurofilament genes NEFL and NEFM (Ex1), were underrepresented in AD compared to control samples”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plaincorrelationaln = 11- Asserted: passes — The authors put it forward as true.
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In the paper
“gene ontology (GO) analysis identified metal ion homeostasis as the top pathway downregulated in microglia”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These Aβ-reactive Serpina3n+Olig2+ cells were markedly enriched in plaque-bearing brain regions”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Proteomic analysis yielded a list of proteins more abundant in CV-5XFAD than in CV brains that were largely concordant with genes identified by snRNA-seq, but with a significant number of additions”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Bulk proteomic analysis validates Trem2-dependent and -independent activation genes at the protein level
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Unsupervised clustering revealed a total of 10 distinct clusters across all samples”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Upregulated phosphopeptides were more typically expressed in neuronal than in glial populations.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Bulk proteomic analysis validates Trem2-dependent and -independent activation genes at the protein level
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The majority of upregulated proteins were most highly expressed in microglia.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Bulk proteomic analysis validates Trem2-dependent and -independent activation genes at the protein level
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of special note, Serpina3n and C4b were among the top 20 most upregulated proteins, validating these as important activation markers.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Bulk proteomic analysis validates Trem2-dependent and -independent activation genes at the protein level
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Ingenuity Pathway Analysis (IPA) of the most highly upregulated proteins identified immune pathways overwhelmingly as the most significant in this regard”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Bulk proteomic analysis validates Trem2-dependent and -independent activation genes at the protein level
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“re-clustering of microglia from 15-month-old mice revealed that one distinct sub-cluster was exclusively represented in 5XFAD mice and enriched in DAM genes”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > DAM signature is Trem2-dependent at early and late stages of Aβ accumulation
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Most clusters were represented similarly in AD and control samples”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plainn = 11- Asserted: passes — The authors put it forward as true.
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In the paper
“Nuclei distribution of TREM2 R62H AD samples was more similar to TREM2 CV AD than to controls.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Other genes previously reported to be up-regulated in human AD but not as part of the DAM signature, including SORL1, A2M, and CHI3L1, were also highly upregulated”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The majority of microglia-expressed proteins were less abundant in Trem2−/− 5XFAD and R47H-5XFAD brains than in CV-5XFAD brains.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Bulk proteomic analysis validates Trem2-dependent and -independent activation genes at the protein level
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“phosphopeptides that increased most dramatically from CV to CV-5XFAD generally did not originate from proteins with the greatest total-level changes, with the exception of Spp1”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Bulk proteomic analysis validates Trem2-dependent and -independent activation genes at the protein level
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we found significantly higher expression of Cst7, Csf1, MHC-I (H2-K and b2m), among other genes, in 5XFAD than in Trem2−/− 5XFAD microglia”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > DAM signature is Trem2-dependent at early and late stages of Aβ accumulation
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MHCII, TREM2, CD68, and APOE were among the few DAM gene homologues upregulated in human AD samples compared to controls”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This sub-cluster specifically expressed DAM genes”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > DAM signature is Trem2-dependent at early and late stages of Aβ accumulation
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, genes expressed by oligodendrocytes, astrocytes, and endothelial cells were also substantially represented at the protein level”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Bulk proteomic analysis validates Trem2-dependent and -independent activation genes at the protein level
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The increase in oligodendrocytes that express Serpina3n in 5XFAD brains was confirmed by staining with CA2 as an alternative oligodendrocyte marker”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we observed downregulation of many neuronal genes, albeit with a fold change less than 1.5”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“proteins such as the neurotrophic factor Midkine25, were found to be highly upregulated, despite being unchanged in our snRNA-seq analysis.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Bulk proteomic analysis validates Trem2-dependent and -independent activation genes at the protein level
What the sources say
- Not checked yetcites [25] Winkler, C. & Yao, S. The midkine family of growth factors: diverse roles in nervous system formation and maintenance. Br. J. Pharmacol. 171, 905–912 (2014). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which was even more marked in mice at 15 months of age”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“A heatmap of oligodendrocyte-specific gene expression in AD versus controls revealed significant downregulation of genes that promote myelination through modification of the actin cytoskeleton, such as Stathmin 4 (STMN4)34, axonal guidance, like Semaphorin3B (SEMA3B)35, and differentiation of precursor cells into mature myelin-forming cells (MIR219A2)36”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > AD-reactive oligodendrocytes reflect functional and metabolic adaptation to axonal degeneration
What the sources say
- Not checked yetcites [34] Richter-Landsberg, C. The cytoskeleton in oligodendrocytes. Microtubule dynamics in health and disease. J. Mol. Neurosci. MN 35, 55–63 (2008). source
- Not checked yetcites [35] Mecollari, V., Nieuwenhuis, B. & Verhaagen, J. A perspective on the role of class III semaphorin signaling in central nervous system trauma. Front. Cell. Neurosci. 8, 328 (2014). source
- Not checked yetcites [36] Wang, H. et al. miR-219 Cooperates with miR-338 in myelination and promotes myelin repair in the CNS. Dev. Cell 40, 566–582.e5 (2017). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The human homologues of mouse Serpina3n and C4b, SERPINA3 and C4B, which were upregulated in reactive oligodendrocytes in the 5XFAD model, were predominantly expressed in astrocytes rather than oligodendrocytes in the human brain”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > AD-reactive oligodendrocytes reflect functional and metabolic adaptation to axonal degeneration
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AD R62H carriers clustered more closely with AD CV carriers than with controls, especially within the non-neuronal clusters”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Brain signatures of AD carrying TREM2 variants demonstrate reduced microglial response
plaincorrelationaln = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“some microglial AD-reactive genes were downregulated in AD R62H carriers (TREM2, HLA-DRA and CHI3L1)”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Brain signatures of AD carrying TREM2 variants demonstrate reduced microglial response
plaincorrelationaln = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“genes enriched in Oligo1 and Micro1 (down-regulated in AD) corresponded to genes previously identified as downregulated during human aging and early onset AD patients from public datasets”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > AD-reactive oligodendrocytes reflect functional and metabolic adaptation to axonal degeneration
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pathway analysis documented an increase in activated microglia and neuronal functional pathways in both the BRI and Rush cohorts”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Whole brain nCounter mRNA analysis corroborates AD glial signatures and verifies neuronal loss
plaincorrelationaln = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“a subpopulation of astrocytes evident in controls was not present in AD”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > The astrocyte signature indicates increase in glial scaring and loss of metabolic coordination between neurons and astrocytes
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“moreover, SERPINA3 expression was reduced rather than increased in the AD brains”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > AD-reactive oligodendrocytes reflect functional and metabolic adaptation to axonal degeneration
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“genes enriched in Micro0 and Oligo0 (upregulated in AD) correlated with upregulation during aging and early onset AD”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > AD-reactive oligodendrocytes reflect functional and metabolic adaptation to axonal degeneration
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In human AD, we noted clear contraction of a subset expressing a metabolic signature indicative of lipid uptake, storage, oxidation and detoxification”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
In the paper
“these data exposed diminished expression of genes encoding for neurotrophic factors (BDNF), neurotransmitters (ADCYAP1), molecules involved in axon guidance (PLXNC1), plasticity (ARC)39, synaptic vesicles (V-ATPase G subunits (ATP6V1G2) and ion channels (RIMS1) (Fig. 5h,i), indicating neuronal cell death.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Whole brain nCounter mRNA analysis corroborates AD glial signatures and verifies neuronal loss
What the sources say
- Not checked yetcites [39] Dickey, C. A. et al. Selectively reduced expression of synaptic plasticity-related genes in amyloid precursor protein + presenilin-1 transgenic mice. J. Neurosci. 23, 5219–5226 (2003). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the 5XFAD model, astrocytes assumed a very modest Aβ-dependent signature marked by expression of Gfap.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 5XFAD mouse model recapitulates key aspects of human AD relevant to glial and neuronal transcriptional responses.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NanoString nCounter mRNA analyses documented a marked decrease in the expression of several microglia genes, including IRF8, HLA-DRA, and AIF1, in the R47H samples”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Brain signatures of AD carrying TREM2 variants demonstrate reduced microglial response
plaincorrelationaln = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AD patients carrying R62H and those carrying CV TREM2 had very similar transcriptional profiles, as seen by t-SNE plot”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Brain signatures of AD carrying TREM2 variants demonstrate reduced microglial response
plainn = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This sub-cluster was highly enriched for genes down-regulated in AD astrocytes (Fig. 5b), which include those controlling free-fatty acid (FA) transport (FABP5), storage in lipid droplets (HILPDA), as well as oxidation and detoxification of the resulting reactive oxygen species (SOD2)”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > The astrocyte signature indicates increase in glial scaring and loss of metabolic coordination between neurons and astrocytes
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NanoString analysis corroborated a mild reduction in expression of microglial genes such as TMEM119, IL10RA and HPGDS in the R62H samples compared to CV AD samples”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Brain signatures of AD carrying TREM2 variants demonstrate reduced microglial response
plaindirectn = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Astrocyte signatures also markedly differed between the mouse model and human AD.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 5XFAD mouse model recapitulates key aspects of human AD relevant to glial and neuronal transcriptional responses.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All AD patients, R62H carriers and CV carriers, had similar numbers of microglia.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Brain signatures of AD carrying TREM2 variants demonstrate reduced microglial response
plainn = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“not much difference was seen in astrocytes when comparing R62H to CV samples”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Brain signatures of AD carrying TREM2 variants demonstrate reduced microglial response
plainn = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During human AD, microglia acquire a quite distinct signature characterized by increased expression of “homeostatic” genes (TMEM119, CX3CR1, P2RY12) along with genes absent in the DAM signature, such as A2M, CHI3L1 and IRF8.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In neuronal populations, human AD samples showed diminished expression of genes controlling neurotransmission (ADCYAP1), plasticity (ARC), synaptic vesicles (ATP6V1G2), ion channels (RIMS1), and axon guidance (PLXNC1).”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In parallel, astrocytes upregulated a signature indicative of extracellular matrix protein synthesis related to glial scarring.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
In the paper
“Our human data are partially concordant with a recent study examining human AD and control samples by snRNA-seq20.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
What the sources say
- Not checked yetcites [20] Mathys, H. et al. Single-cell transcriptomic analysis of Alzheimer’s disease. Nature 570, 332–337 (2019). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also distinguish additional genes upregulated in AD”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the 5XFAD model, oligodendrocytes adopted a reactive signature including C4b and Serpina3n that was not evident in human AD samples”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 5XFAD mouse model recapitulates key aspects of human AD relevant to glial and neuronal transcriptional responses.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No reads from Trem2−/− and Trem2−/− 5XFAD mice align to Trem2 exon2.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, we documented a measurable impact of the human R47H and R62H variants on microglia responses”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In parallel, oligodendrocytes elevated expression of genes sensitive to changes in pH and electrolytes (CA2), osmotic imbalance (SLC38A2), lipid accumulation (MID1IP1), and oxidative stress (SEPP1)”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“a novel astrocyte cluster depleted in AD”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
In the paper
“Several cell type-specific upregulated genes identified by Mathys et al., including MHC class II and APOE in microglia and QDPR, CA2, and SLC38A2 in oligodendrocytes, were also upregulated in our AD samples.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
What the sources say
- Not checked yetcites [20] Mathys, H. et al. Single-cell transcriptomic analysis of Alzheimer’s disease. Nature 570, 332–337 (2019). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“upregulation of certain “homeostatic” microglia genes”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, C4b was particularly effective in inducing Aβ aggregation in vitro.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: In vitro Aβ aggregation induced by C4b is relevant to AD pathogenesis in vivo.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“while astrocyte and oligodendrocyte reactive signatures were not obviously affected.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In human AD, oligodendrocytes expressed fewer transcripts of genes controlling axonal myelination through axon guidance (SEMA3B), rearrangement of actin cytoskeleton (STMN4) and maturation of myelin-forming cells (MIR219A2).”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Clusters 2 and 11 (neuronal) were exclusive to hippocampus”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
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In the paper
“These oligodendrocyte signatures are distinct from those recently associated with multiple sclerosis21 and senescence43.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
What the sources say
- Not checked yetcites [21] Jäkel, S. et al. Altered human oligodendrocyte heterogeneity in multiple sclerosis. Nature 566, 543–547 (2019). source
- Not checked yetcites [43] Zhang, P. et al. Senolytic therapy alleviates Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer’s disease model. Nat. Neurosci. 22, 719–728 (2019). source
plain- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Proteomic analysis recapitulates major findings from snRNA-seq analysis.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Top, up-regulated genes are enriched in Oligo0 and Oligo3 (indicated in Fig.5).”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
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In the paper
“t-SNE projection of all nuclei in AD versus control samples showing the lack of a sub-population of astrocytes in AD.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
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In the paper
“IPA analysis showing pathways upregulated in CV-5XFAD compared to CV mice in proteomics.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelationaln = 312- Asserted: passes — The authors put it forward as true.
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In the paper
“t-SNE plot of re-clustered microglia (from cluster 10) identifying 4 sub-clusters.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Genes enriched in Micro0 and Oligo0 correspond to genes previously identified as upregulated in human aging and early onset AD patients.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Volcano plot showing DEGs of AD vs. control from the BRI cohort.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelationaln = 10- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“t-SNE plot showing the microglia cluster (cluster 10 from Extended Data Fig. 2), expressing microglia genes, such as C1qa, Fcrls, and Tyrobp.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
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In the paper
“t-SNE plots showing the average z-scores of down-regulated genes in astrocytes. Red circle indicates the disappearing population enriched for down-regulated genes.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Genes enriched in Micro1 and Oligo1 correlate with downregulation in aging and early onset AD.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“RT-qPCR from HOG treated with soluble factors (GPNMB or alpha-2-macroglobulin) for 24 hours or a cocktail of cytokines (IL-1β, IL-6, TNFα, IFNα, IFNγ) for 8 hours showing induced C4.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaindirectn = 3- Asserted: passes — The authors put it forward as true.
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In the paper
“Human AD-associated oligodendrocyte and microglia signatures identified by snRNA-seq match public datasets from aging and early onset AD populations.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Cluster 4 (neuronal) was enriched in Trem2−/− 5XFAD cortex.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelationaln = 3- Asserted: passes — The authors put it forward as true.
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In the paper
“NanoString nCounter analysis of two cohorts of AD patients corroborates findings in snRNA-seq.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelationaln = 2- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Bottom, down-regulated genes are enriched in Oligo1 and Oligo2.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“AD-associated human signatures are distinct from that in Aβ mouse models.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plainn = 11- Asserted: passes — The authors put it forward as true.
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In the paper
“Sub-cluster 3 is only present in the 5XFAD sample.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pathway analysis showing the same pathways are differentially regulated in AD brains from Rush (left) and BRI (right).”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelationaln = 2- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IPA analysis showing pathways upregulated in CV-5XFAD compared to CV mice in phospho-proteomics.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelationaln = 270- Asserted: passes — The authors put it forward as true.
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In the paper
“RT-qPCR from human oligodendrocyte cell line (HOG) treated with Aβ oligomers or fibrils at the indicated concentrations for 18 hours showing Aβ directly induces C4.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaindirectn = 3- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Violin plots showing the expression of DAM genes, Cst7, Gpnmb and Spp1, enriched in sub-cluster 3.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelationaln = 266- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“activation of “disease-associated microglia” (DAM) is dependent on TREM2 in mouse models of AD.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
What the sources say
- Not checked yetcites [10] Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290.e17 (2017). source
- Not checked yetcites [15] Wang, Y. et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model. Cell 160, 1061–1071 (2015). source
- Not checked yetcites [17] Song, W. M. et al. Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism. J. Exp. Med. 215, 745 (2018). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Most notably, a hypomorphic variant in the microglial receptor TREM2, R47H, increases the risk of AD several fold, as do other TREM2 variants, such as R62H, although with reduced penetrance14.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
What the sources say
- Not checked yetcites [14] Ulland, T. K. & Colonna, M. TREM2 - a key player in microglial biology and Alzheimer disease. Nat. Rev. Neurol. 14, 667–675 (2018). source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“which may represent dystrophic neurons that accumulate over time as a result of ineffective microglial control of AD pathology due to lack of Trem218,19.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals a Trem2-dependent microgliosis at early stages of Aβ accumulation
What the sources say
- Not checked yetcites [18] Yuan, P. et al. TREM2 haplodeficiency in mice and humans impairs the microglia barrier function leading to decreased amyloid compaction and severe axonal dystrophy. Neuron 90, 724–739 (2016). source
- Not checked yetcites [19] Wang, Y. et al. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. J. Exp. Med. 213, 667–675 (2016). source
hedgedconditionaln = 3- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“further evidence that Aβ pathology induces an expansion of microglia that is partially TREM2-dependent.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals a Trem2-dependent microgliosis at early stages of Aβ accumulation
plaindirectn = 3- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“demonstrating a TREM2 requirement in both mouse and human AD, despite the marked species-specific differences.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Microglia signature was reminiscent of IRF8-driven reactive microglia in peripheral nerve injury.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
What the sources say
- Not checked yetcites [27] Masuda, T. et al. IRF8 is a critical transcription factor for transforming microglia into a reactive phenotype. Cell Rep. 1, 334–340 (2012). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Astrocyte profiles indicated weakened metabolic coordination with neurons.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“remarkably different glial phenotypes were evident in human AD.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
boosted- Asserted: passes — The authors put it forward as true.
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In the paper
“This signature was remarkably similar to the IRF8-driven reactive phenotype that mouse microglia adopt in peripheral nerve injury (PNI)27.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
What the sources say
- Not checked yetcites [27] Masuda, T. et al. IRF8 is a critical transcription factor for transforming microglia into a reactive phenotype. Cell Rep. 1, 334–340 (2012). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Altogether, these results demonstrate that Aβ accumulation in mice is paralleled by an increase in the number and reactive state of oligodendrocytes that may be partially dependent on TREM2, at least at early stages of disease.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We conclude that the impact of Aβ beyond microglia and oligodendrocytes is limited.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Transcriptional changes in neuronal and other non-neuronal populations in response to Aβ are minimal
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting a progressive oligodendrocyte response to Aβ-accumulation.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that the reactive oligodendrocyte response to Aβ pathology may be influenced by microgliosis at early stages of disease.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we characterized an AD-associated signature in microglia, astrocytes and oligodendrocytes that is quite distinct from the AD signature identified in mouse Aβ models.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > AD-reactive oligodendrocytes reflect functional and metabolic adaptation to axonal degeneration
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“AD patients carrying the R47H variant, who have a higher risk (2-4-fold) of developing AD than do R62H carriers.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Brain signatures of AD carrying TREM2 variants demonstrate reduced microglial response
What the sources say
- Not checked yetcites [14] Ulland, T. K. & Colonna, M. TREM2 - a key player in microglial biology and Alzheimer disease. Nat. Rev. Neurol. 14, 667–675 (2018). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“In mice accumulating Aβ, microglia swap their “homeostatic” signature with a DAM signature that is partially Trem2-dependent10,11.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
What the sources say
- Not checked yetcites [10] Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290.e17 (2017). source
- Not checked yetcites [11] Krasemann, S. et al. The TREM2–APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581.e9 (2017). source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that the expression of these genes may no longer be elicited due to axonal degeneration.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > AD-reactive oligodendrocytes reflect functional and metabolic adaptation to axonal degeneration
hedgedconditional- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our multi-pronged analyses of AD pathology in both mouse and human brains demonstrates a remarkable discordance between the transcriptional signatures indicative of cellular responses in human AD and those seen in the 5XFAD mouse model of Aβ accumulation.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
boosted- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Expression of these genes may facilitate metabolic responses to the accumulation of degradation products derived from axonal degeneration.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > AD-reactive oligodendrocytes reflect functional and metabolic adaptation to axonal degeneration
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“This signature evokes the reactive microglia phenotype described in a mouse model of PNI that is driven, at least in part, by IRF827 and MafB42.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
What the sources say
- Not checked yetcites [27] Masuda, T. et al. IRF8 is a critical transcription factor for transforming microglia into a reactive phenotype. Cell Rep. 1, 334–340 (2012). source
- Not checked yetcites [42] Tozaki-Saitoh, H. et al. Transcription factor MafB contributes to the activation of spinal microglia underlying neuropathic pain development. Glia 67, 729–740 (2019). source
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which may be indicate a response to accumulation of degradation products derived from axonal degeneration.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These functions may no longer be elicited due to neuronal loss and axonal degeneration.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This difference may help explain the considerable disparity between human and mouse signatures of reactive glial cells.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The 5XFAD mouse model recapitulates key aspects of human AD relevant to glial and neuronal transcriptional responses.
- It may state two separate claims as one. 53
- Probably not a substantial claim. 55
- The quote only partly states this claim. 1
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“this human AD-associated signature was present in aged controls, and highly upregulated during disease.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the proportion of astrocytes was increased in AD compared to control samples, indicating reactive astrocytosis”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Other DAM gene homologues were either similarly expressed in AD and control samples (TYROBP), not detected (CST7, GPNMB, LPL), or even downregulated (SPP1) in human AD microglia”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“sub-cluster 1 was highly represented in 5XFAD mice, less so in Trem2−/− 5XFAD mice and barely detectable in WT and Trem2−/− mice”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > DAM signature is Trem2-dependent at early and late stages of Aβ accumulation
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that addition of C4b to Aβ42 peptides strongly accelerated aggregation of Aβ; Serpina3n alone modestly promoted aggregation at high Aβ42 concentrations and did not synergize with C4b”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also detected little colocalization of Serpina3n with astrocytes (Extended Data Fig. 4j) and Aβ plaques”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the microglia cluster, genes normally considered as ‘homeostatic” in mouse (TMEM119, P2RY12, CX3CR1) were, in fact, notably upregulated in AD compared to controls (Fig. 4c), along with higher expression of the transcription factor IRF8.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“OPCs strongly upregulated C4b, with a fold change and p-value similar to oligodendrocyte activation genes”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Transcriptional changes in neuronal and other non-neuronal populations in response to Aβ are minimal
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Increased expression of C4b and Serpina3n was partially dependent on Trem2 in 7-month-old (Extended Data Fig. 4a) but not in 15-month-old mice”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“DAM genes, including Cst7, Csf1, Apoe, Trem2, Lpl, Lilrb4a, MHC-I (H2-d1), MHC-II (Cd74), and various cathepsin genes were notably upregulated in 5XFAD compared to WT mice. Homeostatic genes, such as P2ry12, Selplg, Tmem119, and Cx3cr1 were downregulated.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > DAM signature is Trem2-dependent at early and late stages of Aβ accumulation
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Astrocytes upregulated Gfap and C4b, but to a lesser extent than did oligodendrocytes”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Transcriptional changes in neuronal and other non-neuronal populations in response to Aβ are minimal
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We analyzed a total of 66,311 individual nuclei with a median of 1,312 genes per nucleus”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plainn = 66,311- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“overexpression of Irf8 in mouse microglia-like cell cultures upregulated the expression of P2RY12, which was conversely reduced in Irf8−/− cells”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we demarcated 6 sub-clusters (Astro0-5) of astrocytes and confirmed the contraction of Astro3 in AD samples”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > The astrocyte signature indicates increase in glial scaring and loss of metabolic coordination between neurons and astrocytes
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Expression of AD-reactive oligodendrocyte genes was lower in AD R62H carriers than in AD CV carriers, yet was significantly higher in AD R62H carriers than in controls”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Brain signatures of AD carrying TREM2 variants demonstrate reduced microglial response
plaincorrelationaln = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Upregulated genes, such as CA2, marked sub-cluster Oligo3, while downregulated genes such as MIR219A2, delineated clusters Oligo1 and Oligo2.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > AD-reactive oligodendrocytes reflect functional and metabolic adaptation to axonal degeneration
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“R47H brains also had elevated expression of genes involved in oxidative stress and lipid metabolism, along with decreased expression of genes involved in autophagy, growth factor signaling, and neural connectivity”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Brain signatures of AD carrying TREM2 variants demonstrate reduced microglial response
plaincorrelationaln = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“NanoString data confirmed increased expression of microglia IRF8, and oligodendrocyte CA2 in AD compared to controls”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Whole brain nCounter mRNA analysis corroborates AD glial signatures and verifies neuronal loss
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“as well as increased astrocyte expression of EGFR, which has been proposed as a potential receptor for Aβ37, and a regulator of astrocytes in multiple sclerosis38.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Whole brain nCounter mRNA analysis corroborates AD glial signatures and verifies neuronal loss
What the sources say
- Not checked yetcites [37] Wang, L. et al. Epidermal growth factor receptor is a preferred target for treating amyloid-β-induced memory loss. Proc. Natl Acad. Sci. USA 109, 16743–16748 (2012). source
- Not checked yetcites [38] Rothhammer, V. et al. Microglial control of astrocytes in response to microbial metabolites. Nature 557, 724–728 (2018). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AD astrocytes also had elevated expression of genes encoding the proteoglycan NCAN and collagen COL5A3, which were enriched in Astro0 and Astro1”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > The astrocyte signature indicates increase in glial scaring and loss of metabolic coordination between neurons and astrocytes
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“oligodendrocytes upregulated the expression of genes controlling pH and electrolytes (CA2), osmotic imbalance (SLC38A2), lipid accumulation (MID1IP1) and oxidative stress (SEPP1)”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > AD-reactive oligodendrocytes reflect functional and metabolic adaptation to axonal degeneration
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“tSNE plots of snRNA-seq of 7-month-old mouse brain showing cell type specific markers identifying each cluster.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelationaln = 73,419- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster 12 had very low frequency and did not have a clear marker profile and was thus omitted from analysis.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, NanoString analysis revealed that the precise glial and neuronal gene signatures varied slightly between the three distinct cohorts analyzed”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A clear reduction in the expression of genes controlling memory networks was not evident in the 5XFAD mouse model, in which neuronal pathology is limited to neurite dystrophy.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The 5XFAD mouse model recapitulates key aspects of human AD relevant to glial and neuronal transcriptional responses.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Some of these transcriptional changes correspond to protein changes previously detected in the CSF as AD biomarkers (see Supplementary Table 3).”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“t-SNE plot showing 13 distinguished clusters, 0–12, with cell type identities determined by expression of specific markers.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“although both transcripts were detected in human astrocytes.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“t-SNE plot showing expression of NEFL in neuronal clusters, especially in cluster Ex1.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“t-SNE plot showing expression of Pam, a representative gene enriched in cluster 4.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelationaln = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Representative immunofluorescence images of Serpina3n staining in 7-month-old mice of all genotypes showing colocalization of Serpina3n with oligodendrocyte marker CA2.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelationaln = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Representative confocal images showing colocalization of Serpina3n with GFAP+ astrocytes in 15-month-old 5XFAD mice.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelationaln = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“clusters 0 and 6 (neuronal) were exclusive to cortex”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cluster 4 has a lower average number of UMIs compared to other neurons.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Representative confocal images showing colocalization of Serpina3n with X04+ plaques in 15-month-old 5XFAD mice.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelationaln = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“t-SNE plots of human snRNA-seq showing cell type specific markers identifying each cluster.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“t-SNE plots showing expression of IL10RA and HPGDS in human microglia.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plainn = 66,311- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“this suggests that, although delayed by Trem2-deficiency, microgliosis can reach a plateau at late stages of disease when aging becomes the major factor.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals a Trem2-dependent microgliosis at early stages of Aβ accumulation
hedgeddirectn = 3- Asserted: passes — The authors put it forward as true.
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In the paper
“Such activated microglia, which have been referred to as disease-associated microglia (DAM), has a transcriptional signature quite distinct from that of homeostatic microglia that markedly declines in mouse models of AD10,11,12.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
What the sources say
- Not checked yetcites [10] Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290.e17 (2017). source
- Not checked yetcites [11] Krasemann, S. et al. The TREM2–APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581.e9 (2017). source
- Not checked yetcites [12] Mathys, H. et al. temporal tracking of microglia activation in neurodegeneration at single-cell resolution. Cell Rep. 21, 366–380 (2017). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Single nuclei analysis of human AD brain specimens has revealed a microglial transcriptional response that partially recapitulates the mouse DAM signature along with perturbation of oligodendrocytes and myelination that is gender-dependent20.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
What the sources say
- Not checked yetcites [20] Mathys, H. et al. Single-cell transcriptomic analysis of Alzheimer’s disease. Nature 570, 332–337 (2019). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Reactive astrocytosis and microgliosis are secondary cellular responses to pathology that occur in diseased brain regions2 and may have both negative and positive effects3,4.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
What the sources say
- Not checked yetcites [2] De Strooper, B. & Karran, E. The cellular phase of Alzheimer’s disease. Cell 164, 603–615 (2016). source
- Not checked yetcites [3] Heneka, M. T., Golenbock, D. T. & Latz, E. Innate immunity in Alzheimer’s disease. Nat. Immunol. 16, 229–236 (2015). source
- Not checked yetcites [4] Griciuc, A. et al. Alzheimer’s disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron 78, 631–643 (2013). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings suggest that changes in the AD brain are a combination of direct Aβ-mediated pathology and secondary responses by TREM2-dependent activated microglia.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“intraneuronal tau hyperphosphorylation and aggregation ensue, causing neuronal and synaptic dysfunction and cell death1.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
What the sources say
- Not checked yetcites [1] Long, J. M. & Holtzman, D. M. Alzheimer disease: an update on pathobiology and treatment strategies. Cell 179, 312–339 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“loss of TREM2 function in AD mouse models restricts the ability of microglia to surround Aβ plaques15,16, proliferate, and convert to DAM10,15,17, which in turn leads to more profound neuritic dystrophy18,19.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
What the sources say
- Not checked yetcites [15] Wang, Y. et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model. Cell 160, 1061–1071 (2015). source
- Not checked yetcites [16] Jay, T. R. et al. TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models. J. Exp. Med. 212, 287–295 (2015). source
- Not checked yetcites [10] Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290.e17 (2017). source
- Not checked yetcites [17] Song, W. M. et al. Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism. J. Exp. Med. 215, 745 (2018). source
- Not checked yetcites [18] Yuan, P. et al. TREM2 haplodeficiency in mice and humans impairs the microglia barrier function leading to decreased amyloid compaction and severe axonal dystrophy. Neuron 90, 724–739 (2016). source
- Not checked yetcites [19] Wang, Y. et al. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. J. Exp. Med. 213, 667–675 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Oligodendrocyte signatures suggested impaired axonal myelination and metabolic adaptation to neuronal degeneration.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“amyloid beta (Aβ) peptides produced by neurons form extracellular aggregates that initiate disease”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
What the sources say
- Not checked yetcites [1] Long, J. M. & Holtzman, D. M. Alzheimer disease: an update on pathobiology and treatment strategies. Cell 179, 312–339 (2019). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Studies of genetic risk for sporadic AD have suggested that microglia not only respond to disease but modulate disease course13.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
What the sources say
- Not checked yetcites [13] Bohlen, C. J., Friedman, B. A., Dejanovic, B. & Sheng, M. Microglia in brain development, homeostasis, and neurodegeneration. Annu. Rev. Genet. https://doi.org/10.1146/annurev-genet-112618-043515 (2019). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These studies have largely concluded that microglia undergo the most prominent changes in diseased brains, due to a combination of increased microglia numbers along with a robust transcriptional activation signature on a per-microglia basis.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Abstract
What the sources say
- Not checked yetcites [5] Gjoneska, E. et al. Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer’s disease. Nature 518, 365–369 (2015). source
- Not checked yetcites [6] Seyfried, N. T. et al. A multi-network approach identifies protein-specific co-expression in asymptomatic and symptomatic Alzheimer’s disease. Cell Syst. 4, 60–72.e4 (2017). source
- Not checked yetcites [7] Gosselin, D. et al. An environment-dependent transcriptional network specifies human microglia identity. Science 356, eaal3222 (2017). source
- Not checked yetcites [8] Olah, M. et al. A transcriptomic atlas of aged human microglia. Nat. Commun. 9, 539 (2018). source
- Not checked yetcites [9] Masuda, T. et al. Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution. Nature 566, 388–392 (2019). source
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating that both Aβ and Trem2 are required for DAM.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > DAM signature is Trem2-dependent at early and late stages of Aβ accumulation
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“altered iron homeostasis has been associated with senescence29.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
What the sources say
- Not checked yetcites [29] Angelova, D. M. & Brown, D. R. Microglia and the aging brain: are senescent microglia the key to neurodegeneration? J. Neurochem. https://doi.org/10.1111/jnc.14860 (2019). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“SORL1 polymorphisms have been linked to susceptibility to AD28 and CHI3L1 is a prognostic fluid biomarker for preclinical AD26”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Reactive oligodendrocytes secrete C4b and Serpina3n, which may facilitate Aβ aggregation.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > snRNA-seq reveals an Aβ-dependent oligodendrocyte reactive signature
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Altogether, these data suggest that the signature of human microglia in AD is quite distinct from that of DAM in the 5XFAD model10,11: it is reminiscent of the reactive phenotype observed in PNI and may be in part instructed by IRF8.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
What the sources say
- Not checked yetcites [10] Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290.e17 (2017). source
- Not checked yetcites [11] Krasemann, S. et al. The TREM2–APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581.e9 (2017). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These results were highly concordant between the 7-month- and 15-month-old datasets (Fig. 2d) and with previously published single cell RNA-seq data of sorted microglia10,11,12.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > DAM signature is Trem2-dependent at early and late stages of Aβ accumulation
What the sources say
- Not checked yetcites [10] Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290.e17 (2017). source
- Not checked yetcites [11] Krasemann, S. et al. The TREM2–APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581.e9 (2017). source
- Not checked yetcites [12] Mathys, H. et al. temporal tracking of microglia activation in neurodegeneration at single-cell resolution. Cell Rep. 21, 366–380 (2017). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Most samples had a median of over 2,000 UMIs per nucleus”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“likely reflecting neuronal loss associated with AD and consistent with NEFL being identified as an AD biomarker in the cerebrospinal fluid (CSF)26”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Human brain AD gene signatures are distinct from those of the 5XFAD model
What the sources say
- Not checked yetcites [26] Molinuevo, J. L. et al. Current state of Alzheimer’s fluid biomarkers. Acta Neuropathol. (Berl.) 136, 821–853 (2018). source
hedgedconditionaln = 11- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“gene signatures indicative of glial responses and neuronal depletion detected by NanoString in the Rush and the BRI cohorts differed somewhat between the two sets of specimens, likely reflecting differences in the transcriptional and functional profiles of glia and neurons in prefrontal and occipital cortices, respectively.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Whole brain nCounter mRNA analysis corroborates AD glial signatures and verifies neuronal loss
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We validated IRF8 expression in human AD microglia by NanoString and IF and showed that IRF8 drives the expression of microglial markers linked to AD, suggesting that IRF8 is likely a major driver of this signature.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting fewer microglia in the R47H than in the CV TREM2 brain specimens and/or reduced expression of these microglial genes on a per cell basis.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Brain signatures of AD carrying TREM2 variants demonstrate reduced microglial response
hedgedcorrelationaln = 5- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“These extracellular matrix molecules may contribute to glial scarring, probably preventing axonal regeneration31.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > The astrocyte signature indicates increase in glial scaring and loss of metabolic coordination between neurons and astrocytes
What the sources say
- Not checked yetcites [31] McKeon, R. J., Jurynec, M. J. & Buck, C. R. The chondroitin sulfate proteoglycans neurocan and phosphacan are expressed by reactive astrocytes in the chronic CNS glial scar. J. Neurosci. 19, 10778–10788 (1999). source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Overall, the AD astrocyte profile was quite different from that of A1 astrocytes induced by inflammatory mediators released by microglia33, reiterating a lack of bona fide inflammation in the AD brain.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > The astrocyte signature indicates increase in glial scaring and loss of metabolic coordination between neurons and astrocytes
What the sources say
- Not checked yetcites [33] Liddelow, S. A. et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481–487 (2017). source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“likely reflecting loss of metabolic coordination between neurons and astrocytes.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
In the paper
“reduced ADCYAP1 in human CSF and brain specimens has been associated with cognitive decline in mild cognitive impairment due to AD40”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Whole brain nCounter mRNA analysis corroborates AD glial signatures and verifies neuronal loss
What the sources say
- Not checked yetcites [40] Han, P. et al. Association of pituitary adenylate cyclase-activating polypeptide with cognitive decline in mild cognitive impairment due to Alzheimer disease. JAMA Neurol. 72, 333–339 (2015). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Neuronal loss in AD may dampen the need for astrocytic scavenger functions devoted to disposal of neuronal toxic waste.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
In the paper
“NCAN polymorphisms have been associated with bipolar disorder, schizophrenia and major depression32.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > The astrocyte signature indicates increase in glial scaring and loss of metabolic coordination between neurons and astrocytes
What the sources say
- Not checked yetcites [32] Schultz, C. C. et al. Common variation in NCAN, a risk factor for bipolar disorder and schizophrenia, influences local cortical folding in schizophrenia. Psychol. Med. 44, 811–820 (2014). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, the R47H variant seems to have a greater impact than the R62H variant on microglial response to AD pathology, consistent with the relatively higher penetrance of the R47H variant for AD.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Results > Brain signatures of AD carrying TREM2 variants demonstrate reduced microglial response
hedgedcorrelationaln = 5- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“NanoString nCounter analysis was based on multivariate linear regression with Bejamani-Yekutieli adjustment.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Statistics and reproducibility
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“but all samples and data were processed in a high-throughput or automated fashion.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Mice
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A regular expression for phosphorylation was used to perform using linear discriminant analysis (LDA) and set a false discovery rate (FDR) of < 2.5%”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Proteomics and phospho-proteomics
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“PSMs with TMT reporter ion summed signal-to-noise ratios less than 55 were excluded from quantitation.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Proteomics and phospho-proteomics
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“After filtering, 38,230 nuclei were remained.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Single-nucleus RNA-Seq
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The quote only partly states this claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Experiments were repeated two or more times.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Statistics and reproducibility
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“No animals were excluded from analysis.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Mice
plain- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“P values were adjusted based on Bonferroni correction.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Statistics and reproducibility
plain- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“After filtering, a total of 73,419 individual nuclei across all genotypes were remained, with a median of 3,941 UMIs and 2,378 genes per nucleus for downstream analysis.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Single-nucleus RNA-Seq
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“11 age-matched controls”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Human samples
plainn = 11- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Sex was balanced between AD (CV) and control individuals, with 7 females and 4 males in each group; the AD (R62H) group has 5 females and 5 males.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Human samples
plainn = 11- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“reflecting disparate demographics and/or differing regions of the brain from which the samples were obtained.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All statistical analyses for validation assays were performed using GraphPad Prism (v.8) with unpaired Student’s t test or one- or two-way ANOVA with Tukey’s multiple comparisons test.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Statistics and reproducibility
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Peptide-spectrum matches (PSMs) were adjusted to a 1% false discovery rate (FDR)52”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Proteomics and phospho-proteomics
What the sources say
- Not checked yetcites [52] Elias, J. E. & Gygi, S. P. Target-decoy search strategy for mass spectrometry-based proteomics. Methods Mol. Biol. Clifton NJ 604, 55–71 (2010). source
plain- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“After filtering, 66,311 nuclei were remained across 11 AD (CV), 10 AD (R62H) and 11 control samples, with a median of 1,951 UMIs and 1,312 genes per nucleus for downstream analysis.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Single-nucleus RNA-Seq
plainn = 11- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cutoffs for UMI and gene number were determined based on histograms showing cell density as a function of UMI/gene counts.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Single-nucleus RNA-Seq
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“nuclei with mitochondrial content greater than 5 percent were removed.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Single-nucleus RNA-Seq
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For confocal images in Fig. 3 and Extended Data Fig. 4, at least three images per mouse brain were acquired and averaged for quantification.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Statistics and reproducibility
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Defects in some of these molecules have been implicated in impaired memory39 and associated with mild cognitive impairment in AD40.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
What the sources say
- Not checked yetcites [39] Dickey, C. A. et al. Selectively reduced expression of synaptic plasticity-related genes in amyloid precursor protein + presenilin-1 transgenic mice. J. Neurosci. 23, 5219–5226 (2003). source
- Not checked yetcites [40] Han, P. et al. Association of pituitary adenylate cyclase-activating polypeptide with cognitive decline in mild cognitive impairment due to Alzheimer disease. JAMA Neurol. 72, 333–339 (2015). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“confidently localized sites with a AScore > 13 were selected for analysis (p-value < 0.05)54.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Proteomics and phospho-proteomics
What the sources say
- Not checked yetcites [54] Beausoleil, S. A., Villén, J., Gerber, S. A., Rush, J. & Gygi, S. P. A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat. Biotechnol. 24, 1285–1292 (2006). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Investigators were not blinded to experimental groups”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Mice
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Adjusted p-value was calculated based on Bonferroni correction.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Analysis of gene differential expression
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“a potential role for IRF8 in microglia reactivity”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Rests on an assumption: Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
- Rests on an assumption: The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Filtered PSMs were collapsed to a final protein-level FDR of < 2%.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Proteomics and phospho-proteomics
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Nuclei that are duplets or multiplets were filtered out by two steps.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Single-nucleus RNA-Seq
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Together these data expand previous studies in mouse models of Aβ aggregation suggesting a pathogenic role for C4b and Serpina3n23,24,44,45, as well as genetic studies linking the human homologue SERPINA3 to AD risk46”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Discussion
What the sources say
- Not checked yetcites [23] Mucke, L. et al. Astroglial expression of human α1-antichymotrypsin enhances alzheimer-like pathology in amyloid protein precursor transgenic mice. Am. J. Pathol. 157, 2003–2010 (2000). source
- Not checked yetcites [24] Nilsson, L. N. et al. α-1-antichymotrypsin promotes β-sheet amyloid plaque deposition in a transgenic mouse model of Alzheimer’s disease. J. Neurosci. 21, 1444–1451 (2001). source
- Not checked yetcites [44] Hong, S. et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352, 712–716 (2016). source
- Not checked yetcites [45] Ma, J., Yee, A., Brewer, H. B., Das, S. & Potter, H. Amyloid-associated proteins α1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments. Nature 372, 92–94 (1994). source
- Not checked yetcites [46] Kamboh, M. I., Sanghera, D. K., Ferrell, R. E. & DeKosky, S. T. APOE*4-associated Alzheimer’s disease risk is modified by α1-antichymotrypsin polymorphism. Nat. Genet. 10, 486–488 (1995). source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: In vitro Aβ aggregation induced by C4b is relevant to AD pathogenesis in vivo.
In the paper
“PSMs with poor quality, MS3 spectra with TMT reporter ion summed signal-to-noise ratios less than 110 were excluded from quantitation53.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Online Methods > Proteomics and phospho-proteomics
What the sources say
- Not checked yetcites [53] McAlister, G. C. et al. Increasing the multiplexing capacity of TMTs using reporter ion isotopologues with isobaric masses. Anal. Chem. 84, 7469–7478 (2012). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Alignment of reads from Trem2-deficient mice to Trem2 exon1 reflects early transcriptional termination due to deletion of exons 3 and 4 in the design of Trem2 knockout constructs.”
§ Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and - independent cellular responses in Alzheimer’s disease > Extended Data
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Little is known about how TREM2-dependent microglial functions affect the Alzheimer's disease brain as a whole.
“Nonetheless, little is known about how TREM2-dependent microglial functions impact the AD brain as a whole.”
The paper relies on this without support.
Post-mortem human brain tissue processed for snRNA-seq reflects the transcriptional state of the brain before death.
“Post-mortem prefrontal cortical tissues from 11 AD patients with TREM2 common variant (CV), 10 AD patients carrying TREM2 R62H variant, and 11 age-matched controls from the Rush cohort were analyzed by snRNA-seq.”
The paper relies on this without support.
The 5XFAD mouse model recapitulates key aspects of human AD relevant to glial and neuronal transcriptional responses.
“In the 5XFAD model, astrocytes assumed a very modest Aβ-dependent signature marked by expression of Gfap.”
The paper relies on this without support.
The cell clusters identified by snRNA-seq correspond to bona fide astrocytes, oligodendrocytes, microglia, and neurons.
“Nuclei from broad cell types (astrocytes, microglia and oligodendrocytes clusters) were taken and re-clustered to further analyze the sub-clusters in each cell type.”
The paper relies on this without support.
In vitro Aβ aggregation induced by C4b is relevant to AD pathogenesis in vivo.
“Moreover, C4b was particularly effective in inducing Aβ aggregation in vitro.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source doesn’t support the claim as written.
In the citing paper
“resulting in over 100,000 astrocyte nuclei in each brain region with ≈6,000 average total number of reads and ≈2,500 average total number of genes detected, which is orders of magnitude higher than previous studies9–15”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [11]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe cited source doesn’t support the claim as written.
In the citing paper
“In parallel, astrocytes uniquely upregulated DDIT4, PFKP and ADCY8, along with genes that suppress fatty acid metabolism (ANGPTL4) and promote lipid droplet storage of fatty acids (HILPDA), while microglia upregulated multiple glycogen-related genes (GBE1, UGP2 and PYGL)48 (Fig. 4m).”
From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [48]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This signaling pathway seems to be conserved in human microglia (Zhou et al., 2020)”
From Alzheimer's-associated PU.1 expression levels regulate microglial inflammatory response (2021) · cites this paper as Zhou et al., 2020
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Interestingly, when we tested expression of genes that show substantial changes in transgenic mice associated with AD (43,44) a number of aspects of gene expression were mimicked by anti-inflammatory IL-4 stimulation, particularly the increased expression of genes associated with the neurodegenerative signature, including Igf1, Itgax, Clec7a and Arg1 (58,59,61,84,86).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [61]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Stage 2 DAMs (sometimes referred to as TREM2-dependent) are activated microglia that are closely associated with amyloid plaques.42,43”
From TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice (2025) · cites this paper as [42]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For instance, TREM2 is one of the strongest risk factors for AD, and evidence suggests that TREM2 acts to recognize Aβ pathology and direct microglial responses toward the pathology (Guerreiro et al., 2013; Zhou et al., 2020).”
From β-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer’s disease (2024) · cites this paper as Zhou et al., 2020
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Importantly, only a subset, often a mix of A1 and A2 or pan-reactive transcripts, are upregulated in astrocytes from brains of study participants with HD74 or AD75,76, or from several mouse models of acute injuries and chronic diseases of the CNS42,69,76,77.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [76]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“may have confounded previous studies that compared only control and severe AD donors or grouped late- and end-stage donors (Braak stage V/VI) together9–15”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“APOE is greatly upregulated in human AD microglia (HAM) from human AD brains”
From ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease (2022) · cites this paper as Zhou et al 2020
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The top hub gene in the plum3 module—Interferon Regulatory Factor 8 (Irf8)—corresponds to interferon signaling that has recently been identified to be upregulated in microglia from human AD [40].”
From Deletion of Abi3/Gngt2 influences age-progressive amyloid β and tau pathologies in distinctive ways (2022) · cites this paper as [40]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“AD DEGs were consistent with published results both for region-specific DEGs and for DEGs computed jointly over all regions for multiple AD variables, and were further corroborated by comparisons with various independent studies11,12,15,19,47–53”
From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [48]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In the current work, we focus on cholesterol 25-hydroxylase (Ch25h), which is upregulated in DAM only when both Apoe and Trem2 are present (Krasemann et al., 2017; Zhou et al., 2020).”
From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Zhou et al., 2020
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Single-cell transcriptomic analysis carried out in AD human and AD mouse model brain tissue have identified unique signatures of gene expression in microglia in physical proximity to amyloid plaques and tau aggregates, termed DAM (Keren-Shaul et al., 2017; Krasemann et al., 2017; Zhou et al., 2020).”
From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Zhou et al., 2020
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Single-nucleus RNA sequencing (snRNA-seq) data on postmortem samples from AD patients and on samples from AD mice model also revealed that the expression of TREM2 was increased in AD pathology.164,213,214”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [213]
The cited source says what the claim attributes to it.
In the citing paper
“RNA-seq studies using human AD autopsy samples have identified myelin-related transcripts among the top altered gene clusters in patients with AD35,46.”
From Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease (2023) · cites this paper as [35]
The cited source says what the claim attributes to it.
In the citing paper
“Human single nucleus RNA sequencing data from Zhou and colleagues [10] were obtained via the AD Knowledge Portal (https://adknowledgeportal.org) study snRNAseqAD_TREM2.”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“We constructed metacells and performed co-expression network analysis for each major cell type in the human PFC dataset11 using the standard hdWGCNA workflow, yielding distinct network structures and sets of gene modules (Data S2 and S3).”
From hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data (2023) · cites this paper as [11]
The cited source says what the claim attributes to it.
In the citing paper
“We performed consensus co-expression network analysis of microglia from three Alzheimer’s disease (AD) snRNA-seq studies,10,11,12 yielding multiple gene modules corresponding to disease-associated microglia and polygenic risk of AD.”
From hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data (2023) · cites this paper as [11]
The cited source says what the claim attributes to it.
In the citing paper
“Next, we performed consensus co-expression network analysis using microglia integrated from three human AD snRNA-seq datasets,10,11,12 identifying four consensus modules (Figure 6C; Data S1).”
From hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data (2023) · cites this paper as [11]
The cited source says what the claim attributes to it.
In the citing paper
“Recent advancements in scRNA-seq technology enabled in-detail trancriptomic analysis of different cell types and identified unique cellular signatures, specifically in microglia, in AD (36, 37).”
From Deletion of Abi3 gene locus exacerbates neuropathological features of Alzheimer’s disease in a mouse model of Aβ amyloidosis (2021) · cites this paper as [37]
The cited source says what the claim attributes to it.
In the citing paper
“Studying microglia using human cell models such as iPSC-derived cells is vital given the species-specific differences in microglial responses between human and mouse cells27.”
From PLCγ2 regulates TREM2 signalling and integrin-mediated adhesion and migration of human iPSC-derived macrophages (2021) · cites this paper as [27]
The cited source says what the claim attributes to it.
In the citing paper
“we found a similar observation in an independent cohort described by Zhou et al. 35 showing increased expression of SPI1 , TGFB1 and GRN in microglia isolated from the brains of individuals with AD that are heterozygous for the APOE3 and APOE4 alleles (Fig. 7h and Extended Data Fig. 6b,c).”
From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [35]
The cited source says what the claim attributes to it.
In the citing paper
“Analysis of public single-nucleus RNA-seq data 35 of astrocytes from the brains of individuals with AD that are homozygous for the APOE3 allele and those that are heterozygous for the APOE3 and APOE4 alleles confirmed that the percentage of GFAP hi and SERPINA3 + astrocytes is increased in donors that are homozygous for the APOE3 allele compared to in those that are heterozygous for the APOE3 and”
From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [35]
The cited source says what the claim attributes to it.
In the citing paper
“We confirmed Hif1a regulon activity in 54.3% of the cluster (from study51) transcriptionally most similar to DAM microglia13”
From Transcriptional signature in microglia associated with Aβ plaque phagocytosis (2021) · cites this paper as [51]
The cited source says what the claim attributes to it.
In the citing paper
“Previous studies described AD-associated molecular and cellular changes5–15; however, cross-study comparisons are challenging without common cell annotations.”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“To corroborate the results, we harmonized snRNA-seq data and associated donor metadata from the PFC from ten additional AD studies spanning 707 donors5–14.”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“but our sample sizes are similar to those reported in previous publications5–14”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“our sample sizes are similar to those reported in previous publications9–17”
From Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease (2024) · cites this paper as [11]
The cited source says what the claim attributes to it.
In the citing paper
“Also, the reanalyses of snRNAseq and scRNAseq data from wildtype mice (Ximerakis et al., 2019;Zhou et al., 2020) suggest that both Ldh transcripts are expressed markedly less in mature myelinating oligodendrocytes compared to neurons and astrocytes (Figure 2j,k).”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Zhou et al., 2020
The cited source says what the claim attributes to it.
In the citing paper
“A similar C4b and H2-D1-expressing oligodendrocyte population was recently described in mouse models of Aβ pathology (Nugent et al., 2020; Zhou et al., 2020).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Zhou et al., 2020
The cited source says what the claim attributes to it.
In the citing paper
“Dysfunction of oligodendrocytes, the myelinating cells of the CNS, may contribute to AD pathogenesis (Nugent et al., 2020; Zhou et al., 2020).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Zhou et al., 2020
The cited source says what the claim attributes to it.
In the citing paper
“C4b+/H2–D1+ oligodendrocytes have also been observed in models of amyloid pathology (Nugent et al., 2020; Zhou et al., 2020).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Zhou et al., 2020
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“We found that, apart from PSEN2 (which is not essential for gamma secretase function when PSEN1 is present [13]), oligodendrocytes had elevated expression of all of these genes (Fig 1A–1D).”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [10]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“transcripts of amyloid precursor protein (APP) and amyloidogenic enzymes are equally abundant in oligodendrocytes (OLs).”
From Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice (2024) · cites this paper as [12]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“We next analyzed recent snRNA-seq datasets of AD patients from two independent studies28, 33, both showing a specific upregulation of PLXNB1 in astrocytes but not other cell types in human AD brains (Fig. 2B).”
From Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease (2024) · cites this paper as [33]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Additionally, Hif1a was predicted for both 87.8% of XO4+ microglia and a subpopulation of 30% of 5xFAD microglia51”
From Transcriptional signature in microglia associated with Aβ plaque phagocytosis (2021) · cites this paper as [51]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In both datasets, Ldha and Ldhb in particular, but also other glycolysis related genes were expressed at a low rate in OLs in comparison to neurons and astrocytes (Figures 2j,k and S3a,b).”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Zhou et al., 2020
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“To further examine the cellular and regional heterogeneity of the human brain, we developed a scalable method, scdemon, which uses sample decorrelation to annotate both ubiquitous and rare gene expression programs in each major cell type, and used annotated modules to identify functional programs associated with specific pathological variables, including a glycolysis- and energy-metabolism-linked”
From Single-cell multiregion dissection of Alzheimer’s disease (2024) · cites this paper as [48]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Expression of Ch25h is controlled by Trem2 (Zhou et al., 2020; Poliani et al., 2015)”
From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Zhou et al., 2020
Experimental — accuracy not yet measuredIn the citing paper
“In addition to the downregulation of genes involved in synaptic transmission and synapse organization, there is also prominent upregulation of genes involved in cell stress, immune response activation and cell death in PFC of AD patients 257–259.”
From Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications (2022) · cites this paper as [259]
In the citing paper
“APP-overexpressing transgenic mice exhibit an increased thickness of myelin (Xu et al. , 2014) and contain more oligodendrocytes (Zhou et al. , 2020).”
From Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease (2020) · cites this paper as Zhou et al., 2020
In the citing paper
“Analysis of homeostatic and disease-associated microglia (DAM) gene signatures in microglia from 5xFAD mice with impaired meningeal lymphatics revealed higher expression of Apoe, Lyz2, Fth1, Timp2, H2-d1, Axl, Cst7, Spp1 and Lpl (Extended Data Fig. 6e, f and Supplementary Table 2), which are involved in the transition from homeostatic to activated microglia21,26.”
From Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy (2021) · cites this paper as [26]
In the citing paper
“These observations suggest that meningeal lymphatic ablation leads to a loss of homeostatic microglia, and acquisition of the DAM signature (and/or the neurodegenerative microglial signature)21,22,26, all of which is counteracted by passive immunotherapy.”
From Meningeal lymphatics affect microglia responses and anti-Aβ immunotherapy (2021) · cites this paper as [26]
In the citing paper
“Transcriptomic signatures of disease can be studied by snRNA-seq applied to post-mortem brain tissue from patients.”
From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Zhou et al., 2020
In the citing paper
“Differences in gene expression profiles of different microglial populations have been recently described using single cell RNA-seq showing some microglial populations are selectively dependent on Trem2 (58–62).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [61]
In the citing paper
“Itgax/CD11C is an integrin or cell surface antigen, and is up-regulated in a number of recent RNA-seq studies in response to amyloid plaques (58,59,61,84).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [61]
In the citing paper
“Other studies have not revealed obvious phenotypes in young Trem2 R47H expressing mice, or even Trem2 knockout mice, unless they are aged or bred to amyloid mouse models (35,61,85–87).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [61]
In the citing paper
“Recent important studies have also shown that impaired/absent Trem2 function attenuates the microglial response to amyloid pathology by regulating microglial number around plaques, regulating microglial activity, and restricting neuritic damage (37,61,84–87,95–99).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [61]
In the citing paper
“There is increasing evidence that reactive microglia in diseased brains demonstrate a mixed phenotype with expression of pro- or anti-inflammatory and homeostatic markers, particularly showing heterogeneity at the single-cell level, rather than completely reproducing the phenotype obtained from homogenous in vitro polarization studies (58,60,61,100–103).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [61]
In the citing paper
“Indeed, a series of recent studies identified transcriptional signatures in response to AD-associated pathology, neurodegeneration and apoptotic neurons, which were in part dependent on Trem2 and included Igf1, Csf1, Itgax, Clec7a and Arg1, at least in mice (58,59,61,84,86).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [61]
In the citing paper
“For instance, we found substantial region-dependence in the magnitude and timing of C4b expression (Figure 1E), a complement component and major schizophrenia risk factor (Sekar et al., 2016) that is robustly up-regulated in aged mice (Hahn et al., 2020) and models of neurodegeneration (Zhou et al., 2020).”
From Atlas of the aging mouse brain reveals white matter as vulnerable foci (2023) · cites this paper as Zhou et al., 2020
Citations
Cites
Metascape provides a biologist-oriented resource for the analysis of systems-level datasets
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Self-citationIntegrating single-cell transcriptomic data across different conditions, technologies, and species
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Neurotoxic reactive astrocytes are induced by activated microglia
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A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493
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Complement and microglia mediate early synapse loss in Alzheimer mouse models
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Self-citation
Cited by
Sorted by citations
Reactive astrocyte nomenclature, definitions, and future directions
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Microglia states and nomenclature: A field at its crossroads
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Role of neuroinflammation in neurodegeneration development
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Metadata
- Authors
- Zhou, Y., Song, W. M., Andhey, P. S., Swain, A., Levy, T., Miller, K. R., Poliani, P. L., Cominelli, M., Grover, S., Gilfillan, S., Cella, M., Ulland, T. K., Zaitsev, K., Miyashita, A., Ikeuchi, T., Sainouchi, M., Kakita, A., Bennett, D. A., Schneider, J. A., Nichols, M. R., Beausoleil, S. A., Ulrich, J. D., Holtzman, D. M., Artyomov, M. N., & Colonna, M.
- Affiliations
- Washington University in St. Louis (US)
- Bluefin Biomedicine (United States) (US)
- Nanostring Technologies (United States) (US)
- University of Brescia (IT)
- University of Missouri–St. Louis (US)
- University of Wisconsin–Madison (US)
- ITMO University (RU)
- Brain Research Institute, Niigata University (JP)
- Rush University Medical Center (US)
- Corresponding author
- Artyomov, Maxim N.
- Colonna, Marco
- ORCID
- Zhou, Yingyue
- Song, Wilbur M.
- Swain, Amanda
- Levy, Tyler
- Poliani, Pietro L.
- Cominelli, Manuela
- Gilfillan, Susan
- Cella, Marina
- Ulland, Tyler K.
- Zaitsev, Konstantin
- Miyashita, Akinori
- Ikeuchi, Takeshi
- Sainouchi, Makoto
- Kakita, Akiyoshi
- Bennett, David A.
- Schneider, Julie A.
- Nichols, Michael R.
- Beausoleil, Sean A.
- Ulrich, Jason D.
- Holtzman, David M.
- Artyomov, Maxim N.
- Colonna, Marco
- Venue
- Nature Medicine
- Published
- 2020-01-01
- Volume
- 26
- Issue
- 1
- Pages
- 131-142
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC6980793
- OpenAlex
- W2998795963
- Semantic Scholar
- 99ea49ab0c1c1672b94039e5c61e1144b048cb80
- Cited by
- 1,150
- References
- 68
- Citations by year
- 2026: 161 · 2025: 194 · 2024: 193 · 2023: 189 · 2022: 161 · 2021: 162 · 2020: 87
- FWCI
- 58.45
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-05-14)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion, other-oa)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (RF1 AG051485, R21 AG059176, RF1 AG059082, RF1 AG047644)
- Cure Alzheimer’s Fund
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (R01 NS090934)
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (R15 GM119070)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- Alzheimer's disease, TREM2, disease-associated microglia, microglia, oligodendrocytes, astrocytes, glial response, Serpina3n, C4b, myelination, axonal degeneration, species differences, 5xFAD mice, amyloid-beta deposition, single-nucleus transcriptomics
- MeSH terms
- Aged, Alzheimer Disease, Animals, Astrocytes, Axons, Brain, Cell Nucleus, Female, Humans, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Nerve Degeneration, Oligodendroglia, Receptors, Immunologic, Transcription, Genetic, Amyloid beta-Peptides, Microglia, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-04, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-04 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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