The DOI matches its Crossref record; 98 of the 98 references it cites were found in a registry or an index; none of the 74 sources its claims cite is checked for support yet.
Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model
Open accessAbstract
TREM2 is an Alzheimer's disease (AD) risk gene expressed in microglia. To study the role of Trem2 in a mouse model of β-amyloidosis, we compared PS2APP transgenic mice versus PS2APP mice lacking Trem2 (PS2APP;Trem2 ko ) at ages ranging from 4 to 22 months. Microgliosis was impaired in PS2APP;Trem2 ko mice, with Trem2 -deficient microglia showing compromised expression of proliferation/Wnt-related genes and marked accumulation of ApoE. Plaque abundance was elevated in PS2APP;Trem2 ko females at 6–7 months; but by 12 or 19–22 months of age, it was notably diminished in female and male PS2APP;Trem2 ko mice, respectively. Across all ages, plaque morphology was more diffuse in PS2APP;Trem2 ko brains, and the Aβ42:Aβ40 ratio was elevated. The amount of soluble, fibrillar Aβ oligomers also increased in PS2APP;Trem2 ko hippocampi. Associated with these changes, axonal dystrophy was exacerbated from 6 to 7 months onward in PS2APP;Trem2 ko mice, notwithstanding the reduced plaque load at later ages. PS2APP;Trem2 ko mice also exhibited more dendritic spine loss around plaque and more neurofilament light chain in CSF. Thus, aggravated neuritic dystrophy is a more consistent outcome of Trem2 deficiency than amyloid plaque load, suggesting that the microglial packing of Aβ into dense plaque is an important neuroprotective activity. SIGNIFICANCE STATEMENT Genetic studies indicate that TREM2 gene mutations confer increased Alzheimer's disease (AD) risk. We studied the effects of Trem2 deletion in the PS2APP mouse AD model, in which overproduction of Aβ peptide leads to amyloid plaque formation and associated neuritic dystrophy. Interestingly, neuritic dystrophies were intensified in the brains of Trem2 -deficient mice, despite these mice displaying reduced plaque accumulation at later ages (12–22 months). Microglial clustering around plaques was impaired, plaques were more diffuse, and the Aβ42:Aβ40 ratio and amount of soluble, fibrillar Aβ oligomers were elevated in Trem2 -deficient brains. These results suggest that the Trem2-dependent compaction of Aβ into dense plaques is a protective microglial activity, limiting the exposure of neurons to toxic Aβ species.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In PS2APP mice, Trem2 deletion impairs plaque-associated microgliosis and shifts amyloid pathology toward a more diffuse, Aβ42-enriched form, with reduced late-stage plaque load but worse axonal dystrophy and spine loss. The authors conclude that Trem2-dependent microglial activation is mainly neuroprotective in β-amyloidosis and that neuronal pathology is a better readout than plaque load.
Key findings
- Trem2 deletion impaired microglial responses to plaque: reduced Iba1+ clusters, CD68 staining, CD45high microglia, and methoxy-X04+ amyloid-containing microglia across ages; RNAseq found 144 transcripts reduced and only 7 increased in PS2APP;Trem2ko microglia (≥2-fold, adjusted p ≤ 0.05), including impaired proliferation/Wnt-related genes.
- Plaque effects were age- and sex-dependent: plaque load was increased in 6–7 month PS2APP;Trem2ko females, but reduced in 12 month females and 19–22 month males; plaques were more diffuse in Trem2ko brains at all ages tested, and amber cores were reduced in Trem2het and nearly absent in Trem2ko aged males.
- Aβ42:Aβ40 ratio was elevated in PS2APP;Trem2ko brains in both TBS and GuHCl fractions across ages, with increased soluble fibrillar oligomers by OC dot blot; ApoE accumulated in Trem2ko microglia in 12 month females despite no difference in microglial Apoe mRNA.
- Neuronal pathology worsened: plaque-associated Lamp1+ axonal dystrophy and total Lamp1+ area increased from 7 months onward in Trem2ko mice; amino cupric silver degeneration was greater at 12 months in females and 19–22 months in males; CSF NfL was significantly higher in Trem2ko mice, while plasma NfL did not differ; plaque-proximal dendritic spine density was lower in Trem2ko than Trem2wt or Trem2het mice, with spine density ~50% reduced near plaque versus distal segments.
Methods
- Compared PS2APP transgenic mice with PS2APP;Trem2ko mice across ages 4 to 22 months, using single-sex cohorts: females at 4, 6–7, and 12 months; males at 6–7 and 19–22 months, plus a 19–22 month male cohort including Trem2het mice.
- Used histology and whole-slide imaging for plaque, Iba1, CD68, Gfap, Lamp1, ApoE, and silver stains; flow cytometry/FACS for brain-resident myeloid cells; RNAseq of sorted microglia; Aβ40/Aβ42 ELISA; nondenaturing dot blots; two-photon imaging of plaque and dendritic spines; and Simoa NfL measurements in CSF/plasma.
- Main analyses included unpaired t tests, one-way ANOVA with Tukey’s multiple-comparisons, differential expression with voom+limma, GO overrepresentation, and gene set scoring.
Limitations
- Stated in the paper: RNAseq was from bulk sorted brain myeloid cells, not single-cell resolution; the CSF/plasma NfL cohort was not littermates and was assembled specifically for NfL measurements after a peer-review recommendation; aged male numbers were depleted, so available Trem2het mice were included to round out that analysis.
- Evident from the text: findings are from a mouse β-amyloidosis model and may not translate directly to human AD; several cohorts were processed as separate batches, and some flow cytometry/methoxy-X04 analyses used very small n (e.g., n = 3 Trem2wt and n = 2 Trem2ko).
- Evident from the text: the study reports histopathological and biochemical outcomes, not cognitive/behavioral measures, so the functional consequences of the observed neuronal pathology are not directly tested.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Figures
Verification
Claims the paper makes
53 Own result · 42 Not checked yet · 27 Own interpretation · 12 Own method · 5 No basis given
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
“elevated neurofilament-L in the CSF”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
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.
In the paper
“The dependence of these transcripts on Trem2 for their induction in PS2APP microglia was approximately concordant with published data from sorted microglial populations from the 5xFAD model (Wang et al., 2015) (Fig. 2A).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
What the sources say
- Not checked yetcites Wang et al., 2015
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.
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 levels of soluble fibrillar oligomeric Aβ”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
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
“Analysis of confocal z-stack images of cortical tissue from 12 month PS2APP;Trem2ko animals also found a significant reduction in the fraction of Iba1 and methoxy-X04 signals that colocalized with each other (Fig. 1-1).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque-associated microgliosis is impaired in PS2APP;Trem2ko microglia
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.
In the paper
“Applying cutoffs of ≥2-fold change and adjusted p value ≤ 0.05, we observed only 7 transcripts with increased abundance in PS2APP;Trem2ko versus PS2APP;Trem2wt microglia (excluding Treml1, an artifact of the KO cassette insertion) (Kang et al., 2018).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
What the sources say
- Not checked yetcites Kang et al., 2018
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
“neuritic dystrophy histopathology was more marked in PS2APP;Trem2ko mice, even at older ages when total plaque was reduced.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
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
“plaque accumulation was reduced at older ages in both female and male Trem2 KO (PS2APP;Trem2ko) mice compared with age-matched Trem2 WT (PS2APP;Trem2wt) mice.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
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.
In the paper
“We also analyzed recently published microglia RNA-Seq expression profiles from the 5xFAD model (Griciuc et al., 2019) and observed similar Trem2-dependent induction for the nine above-mentioned genes, with the exception of Ptk7 (Fig. 2-2B.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
What the sources say
- Not checked yetcites Griciuc et al., 2019
plaindirect- 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
“Supporting this interpretation, the GO knowledge base identified “positive regulation of canonical Wnt signaling pathway” as a biological process overrepresented (fold enrichment = 10.3, FDR = 0.026) among the 144 transcripts with ≥2-fold reduced abundance in PS2APP;Trem2ko microglia (Fig. 2-2A, with six positive factors in Wnt signaling showing reduced expression including Fzd9 (Karasawa et al.,”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
plaindirect- 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
“plaque morphology was more diffuse”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
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 contrast, 144 transcripts (excluding Trem2) showed reduced abundance in PS2APP;Trem2ko compared with PS2APP;Trem2wt microglia using the same cutoffs (Fig. 2A; for extended data table of genome-wide expression values for each sample and summary statistics for differential gene expression, see Fig. 2-1.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
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.
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
“PS2APP;Trem2ko brains showed reduced staining for CD68 marking active microglial lysosomes by IHC”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque-associated microgliosis is impaired in PS2APP;Trem2ko microglia
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.
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
“Trem2-deficient microglia showing compromised expression of proliferation/Wnt-related genes”
- Also stated in: § Introduction · plain
“By RNAseq, we observed that proliferation-related transcripts in PS2APP;Trem2ko microglia were reduced, particularly those encoding certain components and regulators of Wnt-related signaling.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Abstract
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.
- Also stated in: § Introduction · plain
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
“reduced percentage of methoxy-X04+ (amyloid-containing) microglia by flow cytometry”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque-associated microgliosis is impaired in PS2APP;Trem2ko microglia
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.
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
“reduced percentage of CD45high (“activated”) microglia by flow cytometry”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque-associated microgliosis is impaired in PS2APP;Trem2ko microglia
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.
In the paper
“We also observed less induction of the Proliferation module in Trem2ko microglia expression profiles from the 5xFAD model (Griciuc et al., 2019) (Fig. 2-2C).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
What the sources say
- Not checked yetcites Griciuc et al., 2019
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
“Supporting this interpretation, the GO knowledge base identified “positive regulation of canonical Wnt signaling pathway” as a biological process overrepresented (fold enrichment = 10.3, FDR = 0.026) among the 144 transcripts with ≥2-fold reduced abundance in PS2APP;Trem2ko microglia (Fig. 2-2A, with six positive factors in Wnt signaling showing reduced expression including Fzd9 (Karasawa et al.,”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
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
“Here we report that the effects of Trem2 deficiency on plaque load varied with age and sex”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
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.
None of the sources cited for this claim have been checked yet.
In the paper
“The majority of these transcripts showed upregulation in microglial expression profiles from the PS2APP model (Friedman et al., 2018) and other models of β-amyloid pathology (Orre et al., 2014; Wang et al., 2015) compared with nontransgenic mice (Fig. 2A).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
What the sources say
- Not checked yetcites Friedman et al., 2018
- Not checked yetcites Orre et al., 2014
- Not checked yetcites Wang et al., 2015
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 Aβ42:Aβ40 ratio was elevated”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
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
“Four of the eight most starkly reduced transcripts (in terms of fold change) in PS2APP;Trem2ko microglia are regulators of canonical Wnt signaling or proliferation (Dkk2, Wif1, Ctnna3, and Asb11) (Fig. 2B).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
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
“We also observed reductions in total Iba1 and Gfap staining at the later ages”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque-associated microgliosis is impaired in PS2APP;Trem2ko microglia
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.
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
“Microgliosis was impaired in PS2APP;Trem2ko mice”
- Also stated in: § Plaque-associated microgliosis is impaired in PS2APP;Trem2ko microglia · plain
“We found a stark reduction in Iba1+ microglial clusters in PS2APP;Trem2ko mice at 4, 6–7, 12, and 19–22 months compared with PS2APP;Trem2wt (Fig. 1A,B).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Abstract
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.
- Also stated in: § Plaque-associated microgliosis is impaired in PS2APP;Trem2ko microglia · plain
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
“Second, the total Lamp1+ area was also increased from 7 months onward in PS2APP;Trem2ko brain sections (Fig. 7D), indicating that total axonal damage was exacerbated at later ages despite the reduced plaque burden.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
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.
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 effect of Trem2 deletion on the induction of the LPS-related and Interferon-related modules was observed.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
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
“The methoxy-X04/Iba1 costain showed that microglial association with plaque was severely compromised in PS2APP;Trem2ko brains at all examined ages (Fig. 7A,B), corroborating our earlier Iba1 immunohistochemical stains that measured microglial clustering.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
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
“We did not observe any effect of Trem2 deletion on the low levels of plaque deposition detected at the earliest stage examined (4 months).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque load is reduced in aged PS2APP;Trem2ko mice
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
“Using an algorithm based on X-34 signal intensity to quantify the degree of plaque diffuseness, we observed that plaque morphologies were significantly more diffuse in PS2APP;Trem2ko brains in both sexes at all ages tested (Fig. 4B).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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
“Notably, the Aβ42:Aβ40 ratio was higher in PS2APP;Trem2ko than in PS2APP;Trem2wt brains, in both TBS and GuHCl fractions across ages (Fig. 5A,B).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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
“We observed similar results in distinct cohorts of 6 month females and 8 month males by in vivo labeling of plaque using methoxy-X04 injection, followed by fixation and two-photon imaging of intact somatosensory cortex (Fig. 3-1).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque load is reduced in aged PS2APP;Trem2ko mice
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.
None of the sources cited for this claim have been checked yet.
In the paper
“First, on a per plaque basis, axonal dystrophy was exacerbated from 7 months onward in PS2APP;Trem2ko mice (Fig. 7C), similar to findings in other β-amyloid models (Wang et al., 2016; Yuan et al., 2016).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
What the sources say
- Not checked yetcites Wang et al., 2016
- Not checked yetcites Yuan et al., 2016
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.
None of the sources cited for this claim have been checked yet.
In the paper
“As expected, the Neurodegeneration-related gene set, which overlaps with the so-called DAM (Keren-Shaul et al., 2017) and MGnD (Krasemann et al., 2017) genes but relates more specifically to neurodegenerative disease models, was notably impaired in PS2APP;Trem2ko microglia (Fig. 2D; Fig. 2-3).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
What the sources say
- Not checked yetcites Keren-Shaul et al., 2017
- Not checked yetcites Krasemann et al., 2017
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.
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 ApoE immunostaining pattern was especially prominent in, but not limited to, the hippocampal subiculum where plaque tends to first deposit (Fig. 6B).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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
“At the mRNA level, we did not detect a difference in Apoe expression between PS2APP;Trem2wt and PS2APP;Trem2ko microglia (Fig. 6E; see also Fig. 2E).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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
“Instead of ApoE labeling being diminished, we observed microglia in PS2APP;Trem2ko mice to be markedly laden with ApoE (Fig. 6C,D), suggesting that Trem2-deficient microglia exhibit deficits in lipid clearance.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Although we were blinded to Trem2 genotype, there was an obvious difference in plaque appearance between PS2APP;Trem2wt and PS2APP;Trem2ko brains, with X-34+ structures in PS2APP;Trem2ko brains looking more splayed and less compact (Fig. 4A), similar to descriptions of Trem2-dependent plaque alterations in other β-amyloid models (Wang et al., 2016; Yuan et al., 2016).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
What the sources say
- Not checked yetcites Wang et al., 2016
- Not checked yetcites Yuan et al., 2016
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
“At this age, the Campbell-Switzer stain also revealed a distinctive pattern of “amber core” amyloid staining in PS2APP brains (Fig. 3C), thought to represent a mature form of highly condensed plaque.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque load is reduced in aged PS2APP;Trem2ko mice
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
“Degenerating neurites detected by this stain were more abundant in PS2APP;Trem2ko brains of the 12 month female and 19–22 month male cohorts (Fig. 8A,B).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
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
“An intermediate reduction in plaque load was observed in Trem2 heterozygous (PS2APP;Trem2het) mice at 19–22 months (the only age where heterozygous mice were analyzed) (Fig. 3A).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque load is reduced in aged PS2APP;Trem2ko mice
plaindirect- 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
“Similar respective trends were also seen when staining with the prefibrillar Aβ oligomer antibody A11 and pan-reactive 4G8 Aβ antibody (data not shown).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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
“PS2APP;Trem2ko mice had significantly greater NfL levels in the CSF compared with PS2APP;Trem2wt mice (Fig. 8C), consistent with the measures of increased axonal dystrophy that were observed by histopathology in Trem2-deficient females at this age.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
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
“Spine density was ∼50% reduced on plaque-proximal dendrite segments relative to distal dendrite segments from the same animals.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
plaincorrelationalSingle case- 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
“Perhaps surprisingly, we did not observe a difference in plasma NfL levels between genotypes (Fig. 8C), suggesting that CSF NfL measurements better represent ongoing neuronal damage or degeneration in the CNS than plasma measurements.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
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.
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
“our observation that the Aβ42:Aβ40 ratio declines as the mice age, particularly in the insoluble fraction”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > 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.
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
“Transcriptional induction of the neurodegeneration-related modules, the proliferation module, and certain genes related to Wnt regulation were impaired in PS2APP;Trem2ko microglia.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > 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.
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
“plaques in PS2APP;Trem2ko brains displayed a more diffuse morphology than in PS2APP;Trem2wt brains.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > 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.
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
“Trem2 deletion also increased the amount of NfL detected in CSF.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Discussion
plaindirect- 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
“measurements of neuronal pathology are more informative than plaque load as readouts of microglial modulation in models of β-amyloidosis.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
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.
None of the sources cited for this claim have been checked yet.
In the paper
“The entirety of these changes is approximately equivalent to the so-called DAM (Keren-Shaul et al., 2017) or MgND (Krasemann et al., 2017) microglial activation profiles.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
What the sources say
- Not checked yetcites Keren-Shaul et al., 2017
- Not checked yetcites Krasemann et al., 2017
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 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
“Therefore, their reduced expression in PS2APP;Trem2ko microglia is another manifestation of the impaired microglial response to β-amyloid pathology.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
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.
None of the sources cited for this claim have been checked yet.
In the paper
“These observations were consistent with reports of Trem2 deletion in other β-amyloidosis models (Jay et al., 2015; Wang et al., 2015, 2016; Yuan et al., 2016; Parhizkar et al., 2019) and suggested that Trem2 deficiency impairs the ability of microglia to engage plaques and phagocytose Aβ filbrils/aggregates.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque-associated microgliosis is impaired in PS2APP;Trem2ko microglia
What the sources say
- Not checked yetcites Jay et al., 2015
- Not checked yetcites Wang et al., 2015, 2016
- Not checked yetcites Yuan et al., 2016
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.
- Rests on an assumption: The effects of Trem2 deletion in PS2APP mice are mediated specifically by microglial Trem2 rather than by other Trem2-expressing myeloid cells or non-myeloid cells.
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 amber cores were reduced in PS2APP;Trem2het and nearly absent in PS2APP;Trem2ko brains, indicating that Trem2-dependent microglial activity is essential for the formation of these particular amyloid structures.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque load is reduced in aged PS2APP;Trem2ko mice
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.
- Rests on an assumption: Amber core amyloid staining represents a mature form of highly condensed plaque.
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 staining pattern appeared very similar to the Lamp1 stain, with “bouquets” of argyrophilic structures presumably surrounding plaques throughout the cortex and hippocampus. Staining was also observed in relevant white matter tracts, such as the corpus callosum, perforant path, and fornix, suggesting that degenerating axonal processes are not restricted to dystrophic neurites around”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
hedged- 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
“This is consistent with the idea that the diffuse plaque structures and elevated Aβ42:Aβ40 ratio in Trem2ko brains are more damaging to surrounding axons than the more compacted, Aβ40-enriched plaques in PS2APP;Trem2wt brains.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
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.
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
“Second, the total Lamp1+ area was also increased from 7 months onward in PS2APP;Trem2ko brain sections (Fig. 7D), indicating that total axonal damage was exacerbated at later ages despite the reduced plaque burden.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
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.
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 results suggest that, in the absence of Trem2, the increased Aβ42:Aβ40 ratio enhances the potential shift of soluble Aβ to a fibrillar oligomeric form.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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.
In the paper
“Overall, our results are similar to previous analysis of the 5xFAD model, in which the microglial induction of many DAM genes showed substantial Trem2 dependence whereas the downregulation of so-called microglial “homeostatic” genes appeared largely Trem2-independent (Keren-Shaul et al., 2017).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
What the sources say
- Not checked yetcites Keren-Shaul et al., 2017
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Although two groups have reported reductions in microglial Apoe expression in the APPPS1 model when Trem2 is deleted (Krasemann et al., 2017; Parhizkar et al., 2019), this does not appear to be a typical feature of Trem2 deficiency in β-amyloidosis models since previous analyses in the 5xFAD model observed Trem2-independent Apoe induction in either bulk microglia microarray (Fig. 6F) (Wang et al.,”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
What the sources say
- Not checked yetcites Krasemann et al., 2017
- Not checked yetcites Parhizkar et al., 2019
- Not checked yetcites Wang et al., 2015
hedged- 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
“These data strongly suggest that the Trem2-dependent clustering of microglia and their functions around plaque serve to mitigate the neurotoxic effects of Aβ.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
boosteddirect- 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 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
“Instead of ApoE labeling being diminished, we observed microglia in PS2APP;Trem2ko mice to be markedly laden with ApoE (Fig. 6C,D), suggesting that Trem2-deficient microglia exhibit deficits in lipid clearance.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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.
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
“Thus, again, axonal damage was exacerbated in Trem2-deficient mice from older ages despite the fact that plaque accumulation was reduced.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
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.
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
“Presumably as a consequence of the impaired microglial response around plaque, plaques in PS2APP;Trem2ko brains displayed a more diffuse morphology than in PS2APP;Trem2wt brains.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > 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.
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
“Trem2-mediated microgliosis facilitates the consolidation of β-amyloid into a highly compacted, less damaging form.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > 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.
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
“is consistent with the accumulation of compact plaques in size and number over time in the brains of PS2APP mice.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > 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.
In the paper
“a new report indicates that this effect is further magnified in Trem2-deficient mice (Leyns et al., 2019).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Discussion
What the sources say
- Not checked yetcites Leyns et al., 2019
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 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
“Thus, Trem2 is not required for microglia-mediated dendritic spine loss around plaque; and indeed, Trem2 seems to hedge against synapse loss.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
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.
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
“The form of β-amyloid in the brain is more critical than the amount”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > 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 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
“Thus, Trem2 is not required for microglia-mediated dendritic spine loss around plaque; and indeed, Trem2 seems to hedge against synapse loss.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
plainn = 6- 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 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
“Perhaps surprisingly, we did not observe a difference in plasma NfL levels between genotypes (Fig. 8C), suggesting that CSF NfL measurements better represent ongoing neuronal damage or degeneration in the CNS than plasma measurements.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
hedgedcorrelational- 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 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
“helps explain why cognitive decline correlates better with tau pathology and synapse loss than with brain amyloid detection.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Discussion
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.
- Rests on an assumption: Cognitive decline correlates better with tau pathology and synapse loss than with brain amyloid detection.
None of the sources cited for this claim have been checked yet.
In the paper
“In β-amyloid models, the reduction in synapse number requires the presence of microglia since depleting the microglial cell population largely prevents loss of synaptic density (Olmos-Alonso et al., 2016; Spangenberg et al., 2016).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
What the sources say
- Not checked yetcites Olmos-Alonso et al., 2016
- Not checked yetcites Spangenberg et al., 2016
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.
In the paper
“Given that Aβ40 is more easily incorporated into existing dense plaque structures than Aβ42 (Condello et al., 2015)”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Discussion
What the sources say
- Not checked yetcites Condello et al., 2015
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.
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
“Together, these findings suggest that the form of microglial activation brought on by Aβ-related pathologies (the DAM state, or at least the Trem2-dependent component of it) protects neurons by limiting Aβ-induced neuronal injury.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Discussion
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.
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 exacerbated axonal dystrophy and dendritic spine loss observed around plaque in PS2APP;Trem2ko mice imply that Trem2-dependent microglial activity is fundamentally neuroprotective in β-amyloid-driven models of AD-like pathology.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
boosteddirectn = 6- 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. 42
- The quote only partly states this claim. 1
- Probably not a substantial claim. 29
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
“Trem2-deficient microglia showing compromised expression of proliferation/Wnt-related genes and marked accumulation of ApoE.”
- Also stated in: § Introduction · plain
“Additional analyses of PS2APP;Trem2ko mice at 12 months of age revealed ApoE-laden microglia”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Abstract
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. The quote only partly states this claim.
- Also stated in: § Introduction · plain
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 GO biological processes implicated as being downregulated in PS2APP;Trem2ko microglia included positive regulation of bone resorption (fold enrichment = 24.6, FDR = 0.030), protein kinase B signaling (fold enrichment = 16.2, FDR = 0.047), negative regulation of tumor necrosis factor production (fold enrichment = 14.1, FDR = 0.026), positive regulation of smooth muscle cell migration (fold”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
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
“In PS2APP compared with nontransgenic microglia, several of these gene sets were upregulated, including the Neurodegeneration-related, Interferon-related, Proliferation, and LPS-related modules, whereas the Microglia and Brain Myeloid modules that typify microglia in their “homeostatic” or “resting” state were modestly but significantly downregulated (Fig. 2D; Fig. 2-3.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
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
“For instance, even though only 5 of 82 genes in the Proliferation module were upregulated strongly enough in PS2APP microglia to reach genome-wide significance (adjusted p ≤ 0.05), the overall expression of the module was clearly enriched compared with microglia from nontransgenic mice (Fig. 2D; Fig. 2-3.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
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
“Again, despite only 2 of 82 genes (Ccna2 and Aspm) showing significant reduction in transcript abundance after correction for genome-wide analysis, the overall induction of the Proliferation module was compromised in PS2APP;Trem2ko microglia (Fig. 2D; Fig. 2-3).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
plaindirect- 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 contrast to the effects of Trem2 deletion on total plaque burden that varied with age or sex, we observed consistent changes in plaque compaction and composition across ages and sexes.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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.
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 expected to see further exacerbation of amyloid plaque load in Trem2-deficient brains at more advanced ages, but, to our surprise, plaque load was reduced in 12 month PS2APP;Trem2ko females and in 19–22 month PS2APP;Trem2ko males compared with PS2APP;Trem2wt mice (Fig. 3A,B).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque load is reduced in aged PS2APP;Trem2ko mice
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.
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 contrast, when we used the pan-reactive 6E10 Aβ antibody to detect total Aβ species in this fraction, the abundance trended slightly downward in PS2APP;Trem2ko mice and correlated negatively with Aβ42:Aβ40 ratio (Fig. 5F–H).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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
“Indeed, using the Campbell-Switzer silver stain to label amyloid plaque (Campbell et al., 1987; Switzer, 2000), we observed that plaque burden was increased in 6–7 month PS2APP;Trem2ko females, and trending upward but not reaching significance in 6–7 month PS2APP;Trem2ko males (Fig. 3A,B).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque load is reduced in aged PS2APP;Trem2ko mice
What the sources say
- Not checked yetcites Campbell et al., 1987
- Not checked yetcites Switzer, 2000
plaindirect- 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.
In the paper
“Unlike the clear requirement of Trem2 for induction of many genes in the Neurodegeneration-related gene set, the downregulation of the Microglia and Brain Myeloid modules that normally occurs during any CNS challenge (Friedman et al., 2018) was not prevented by Trem2 deletion since expression of these modules was similar in PS2APP;Trem2wt and PS2APP;Trem2ko microglia (Fig. 2D; Fig. 2-3).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
What the sources say
- Not checked yetcites Friedman et al., 2018
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
“The elevated Aβ42:Aβ40 ratio in PS2APP;Trem2ko brains resulted more from reduced abundance of Aβ40 than from increased abundance of Aβ42 (Fig. 5-1), although Aβ42 abundance was elevated in the 6–7 month females, coinciding with the increased plaque deposition we observed in that group (Fig. 3A).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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.
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 contrast to the findings of Parhizkar et al. (2019), quantification of plaque-associated ApoE in whole-brain sections found a significant increase in female PS2APP;Trem2ko mice at 6–7 and 12 months of age, but no significant changes in male cohorts at any age tested (Fig. 6A).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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.
In the paper
“Using the conformation-specific OC antibody (Tomic et al., 2009), we detected significantly higher levels of soluble fibrillar Aβ oligomers in the soluble fraction from PS2APP;Trem2ko mice (Fig. 5C,D), and we observed a positive correlation between the amount of OC+ fibrillar oligomers in this fraction and the Aβ42:Aβ40 ratio (Fig. 5E).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
What the sources say
- Not checked yetcites Tomic et al., 2009
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.
In the paper
“Of the 134 genes in this set, 80 showed upregulation in PS2APP versus normal microglia (Friedman et al., 2018), and approximately half of these showed impaired induction in PS2APP;Trem2ko microglia (adjusted p values ≤ 0.05) (Fig. 2E).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
What the sources say
- Not checked yetcites Friedman et al., 2018
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.
In the paper
“In a very recent dataset of bulk microglia RNA-Seq profiles from 5xFAD mice (Griciuc et al., 2019), we did see a twofold decrease in the extent of Apoe induction in Trem2-deficient microglia, but the gene was still highly induced relative to the expression level in microglia from nontransgenic mice (Fig. 6F).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
What the sources say
- Not checked yetcites Griciuc et al., 2019
plaindirect- 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
“The abundance of Aβ peptides rose markedly with age while the Aβ42:Aβ40 ratio declined, particularly in the GuHCl fraction (Fig. 5).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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
“Overall, the staining pattern appeared very similar to the Lamp1 stain, with “bouquets” of argyrophilic structures presumably surrounding plaques throughout the cortex and hippocampus. Staining was also observed in relevant white matter tracts, such as the corpus callosum, perforant path, and fornix, suggesting that degenerating axonal processes are not restricted to dystrophic neurites around”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
hedged- 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
“These amber cores were reduced in PS2APP;Trem2het and nearly absent in PS2APP;Trem2ko brains, indicating that Trem2-dependent microglial activity is essential for the formation of these particular amyloid structures.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque load is reduced in aged PS2APP;Trem2ko mice
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.
It may state two separate claims as one.
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
“The fact that plaques in Trem2-deficient mice are more injurious to adjacent neurites but show weaker labeling with molecular probes (Thioflavin S, methoxy-X04 and X-34) related to those used in the clinic (11C-PiB, 18F-Florbetapir)”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > 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.
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
“preventing the microglial response to Aβ pathology via Trem2 deletion reversed neither axonal dystrophy nor dendritic spine loss around plaque and indeed made both of these pathologies worse.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > 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.
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
“At all ages examined, and in both sexes, microglial clustering around plaque and other measurements of microglial activation were sharply reduced in PS2APP;Trem2ko mice.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > 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.
It may state two separate claims as one.
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
“From 6–7 months onward, axonal injury was magnified in PS2APP;Trem2ko mice, even at later ages when the abundance of argyrophilic amyloid plaques was diminished.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > 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.
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 observed both age- and sex-dependent effects of Trem2 deletion on plaque abundance assessed using the Campbell-Switzer silver stain, with slightly more plaque in PS2APP;Trem2ko females at 6–7 months of age but markedly less plaque in both female and male PS2APP;Trem2ko mice at later ages.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > 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.
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
“Spine density loss in the proximity of plaques was not rescued by Trem2 deletion, but was actually further exacerbated in PS2APP;Trem2ko mice compared with PS2APP;Trem2wt or PS2APP;Trem2het groups (Fig. 9).”
- Also stated in: § Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice · plain
“Spine density near plaque was lower in PS2APP;Trem2ko mice than in PS2APP;Trem2wt or PS2APP;Trem2het mice.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
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.
It may state two separate claims as one.
- Also stated in: § Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice · plain
None of the sources cited for this claim have been checked yet.
In the paper
“Trem2 deletion in amyloidosis models has also been reported to either increase or decrease phosphorylation of the endogenous tau protein (Jay et al., 2015; Wang et al., 2016).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
What the sources say
- Not checked yetcites Jay et al., 2015
- Not checked yetcites Wang et al., 2016
plainconditional- 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
“However, whether Trem2 exerts protective or detrimental functions in mouse models of AD-related neuropathology has been rather unclear (Gratuze et al., 2018; Hansen et al., 2018; Ulland and Colonna, 2018).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
What the sources say
- Not checked yetcites Gratuze et al., 2018
- Not checked yetcites Hansen et al., 2018
- Not checked yetcites Ulland and Colonna, 2018
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
“In transgenic models of cerebral β-amyloidosis, plaque load has been reportedly increased, decreased, or unchanged in mice that lack Trem2, depending on the model, age, and brain region being analyzed (Jay et al., 2015, 2017a; Wang et al., 2015, 2016; Yuan et al., 2016; Parhizkar et al., 2019).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
What the sources say
- Not checked yetcites Jay et al., 2015, 2017a
- Not checked yetcites Wang et al., 2015, 2016
- Not checked yetcites Yuan et al., 2016
hedgedcorrelational- 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
“TREM2 is an Alzheimer's disease (AD) risk gene expressed in microglia.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Abstract
What the sources say
- Not checked yetcites Guerreiro et al., 2013
- Not checked yetcites Jonsson et al., 2013
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Dkk2, Wif1, and Ctnna3 can all negatively regulate Wnt activity (Hsieh et al., 1999; Busby et al., 2004; Gage et al., 2008), whereas Asb11 is important for maintaining progenitor cell activity in multiple cell types (Diks et al., 2006; Tee et al., 2012).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
What the sources say
- Not checked yetcites Diks et al., 2006
- Not checked yetcites Tee et al., 2012
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.
In the paper
“We recently defined a number of gene expression modules that can be used to characterize the diverse ways that microglia respond to environmental and genetic perturbations (Friedman et al., 2018).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
What the sources say
- Not checked yetcites Friedman et al., 2018
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.
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
“All animal care and handling procedures were reviewed and approved by the Genentech Institutional Animal Care and Use Committee and were conducted in full compliance with regulatory statutes, Institutional Animal Care and Use Committee policies, and National Institutes of Health guidelines.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Materials and Methods
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.
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
“MATLAB (The MathWorks) running on a high-performance computing cluster was used for all whole-slide image analyses performed in a blinded manner.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Materials and Methods
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
“Images were collected and processed blind to genotypes.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Materials and Methods
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.
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
“To avoid the presence of peripheral myeloid cells in the flow analysis and FACS collections, Ccr2+ cells (peripheral monocytes/macrophages) and Ly6g+ cells (neutrophils) were excluded.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Materials and Methods
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.
Probably not a substantial claim.
In the paper
“PS2APP mice develop amyloid plaque and attendant gliosis pathologies that increase with age, with female mice accumulating the pathology more rapidly than males (Ozmen et al., 2009).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
What the sources say
- Not checked yetcites Ozmen et al., 2009
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. 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
“All steps were performed on ice or at 4°C to prevent artifactual microglial activation.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Materials and Methods
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.
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
“indicative of reduced extents of microgliosis and astrogliosis, respectively, in PS2APP;Trem2ko mice”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque-associated microgliosis is impaired in PS2APP;Trem2ko microglia
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.
None of the sources cited for this claim have been checked yet.
In the paper
“The acquisition of the DAM state is Trem2-dependent in mouse models of AD, amyotrophic lateral sclerosis, and demyelinating disease (Poliani et al., 2015; Wang et al., 2015; Keren-Shaul et al., 2017; Krasemann et al., 2017).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
What the sources say
- Not checked yetcites Poliani et al., 2015
- Not checked yetcites Wang et al., 2015
- Not checked yetcites Keren-Shaul et al., 2017
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.
In the paper
“In the hTau model (Andorfer et al., 2003), Trem2 deletion increased the amounts of tau phosphorylation and aggregation detected (Bemiller et al., 2017).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
What the sources say
- Not checked yetcites Bemiller et al., 2017
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.
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 images, segmentation overlays, and data were reviewed by a pathologist.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Materials and Methods
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Dkk2, Wif1, and Ctnna3 can all negatively regulate Wnt activity (Hsieh et al., 1999; Busby et al., 2004; Gage et al., 2008), whereas Asb11 is important for maintaining progenitor cell activity in multiple cell types (Diks et al., 2006; Tee et al., 2012).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Trem2-dependent induction of the proliferation and neurodegeneration-related gene expression modules
What the sources say
- Not checked yetcites Hsieh et al., 1999
- Not checked yetcites Busby et al., 2004
- Not checked yetcites Gage et al., 2008
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. 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
“CD45low and CD45high gates were defined using a nontransgenic animal as a control to identify microglia in their normal state (CD45low). The same gates were transposed onto cells from PS2APP animals sorted on the same day in the same machine to ensure accuracy and consistency in determining percentages of CD45low and CD45high populations.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Materials and Methods
plainSingle case- 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.
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
“Two sections per animal were stained, with all cohorts stained and analyzed simultaneously.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Materials and Methods
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
“Collectively, our data indicate that Trem2-dependent microglial proliferation and activation attenuate the toxic effects of Aβ toward neurons (i.e., the DAM state is mainly protective)”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
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: The effects of Trem2 deletion in PS2APP mice are mediated specifically by microglial Trem2 rather than by other Trem2-expressing myeloid cells or non-myeloid cells.
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
“Imaging and analysis were performed under blinded conditions.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Materials and Methods
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Transcriptional profiling studies have defined a disease/damage-associated microglial (DAM) activation state that is commonly observed in the brains of neurodegeneration models (Deczkowska et al., 2018; Friedman et al., 2018).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
What the sources say
- Not checked yetcites Deczkowska et al., 2018
- Not checked yetcites Friedman et al., 2018
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.
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
“Generally, animal pairs, including one PS2APP;Trem2wt and one PS2APP;Trem2ko animal, were processed together from perfusion through sorting.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Materials and Methods
hedged- 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
“The 6–7 month cohort of male and female mice was purposely analyzed separately to determine the effects of Trem2 deficiency in each sex since female mice have accelerated amyloid pathology compared with males, and we did not want an analysis of interactions between sex and Trem2 genotype to be confounded by the age-dependent differences in pathology between males and females.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Materials and Methods
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. It may state two separate claims as one.
In the paper
“In contrast, in the PS19 model (Yoshiyama et al., 2007), Trem2 deletion had a protective effect, preventing tau-driven synaptic loss and atrophy in the hippocampus and entorhinal cortex, respectively (Leyns et al., 2017).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Introduction
What the sources say
- Not checked yetcites Leyns et al., 2017
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.
In the paper
“As a control, we spotted hippocampal TBS homogenate supernatant from a PS2APP;Bace1ko animal (Meilandt et al., 2019), in which soluble APP is still produced by α-cleavage while β-cleavage and thus Aβ production are prevented, and demonstrated that the OC antibody had minimal detection, whereas 6E10 still had substantial signal (compare # symbols in Fig. 5C,F and dotted lines in Fig. 5D,G from a PS”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
What the sources say
- Not checked yetcites Meilandt et al., 2019
boostedSingle case- 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
“Together with our observation that total amyloid plaque is reduced in PS2APP;Trem2ko brains at later ages (Fig. 3A), these results suggest that the elevated Aβ42:Aβ40 ratio in Trem2-deficient brains may increase plaque seeding at younger ages (since Aβ42 is more prone to aggregate and deposit than Aβ40) (Klein, 2002) while reducing the incorporation and compaction of Aβ into existing plaques at”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
What the sources say
- Not checked yetcites Klein, 2002
- Not checked yetcites Condello et al., 2015
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.
It may state two separate claims as one.
In the paper
“Overall, our results are reminiscent of a recent study of APPPS1 mice, which showed that Trem2 deletion produced increased seeding of amyloid plaques at early ages but slower rates of amyloid plaque accumulation at later ages (Parhizkar et al., 2019).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Plaque load is reduced in aged PS2APP;Trem2ko mice
What the sources say
- Not checked yetcites Parhizkar et al., 2019
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.
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
“Together, our evidence indicates that microglial Apoe expression is induced by Aβ-driven neuropathology in a largely Trem2-independent manner, and that Trem2-deficient microglia accumulate disproportionately large amounts of ApoE compared with the smaller ApoE puncta observed in normal PS2APP microglia (Fig. 6C).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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.
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
“Thus, Trem2 may both restrict the initial seeding of plaques and promote sequestration and compaction of Aβ into existing plaques.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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.
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
“The intermediate effect of Trem2 heterozygosity on microglial clustering around plaque (Figs. 1A, 7B) and Campbell-Switzer plaque staining (Fig. 3A), but not on plaque diffuseness (Fig. 4B), Aβ42:Aβ40 ratio (Fig. 5A), or neuritic dystrophy (Figs. 7C,D, 8A), suggested that the form rather than the amount of plaque correlates with neuronal damage, and that sufficient microgliosis occurs in PS2APP;T”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
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.
None of the sources cited for this claim have been checked yet.
In the paper
“The elevated Aβ42:Aβ40 ratio and fibrillar Aβ oligomers in PS2APP;Trem2ko brains would seem to be detrimental for neuronal health since Aβ42 oligomers are commonly understood to be the more toxic form of Aβ (Klein, 2002; Haass and Selkoe, 2007).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
What the sources say
- Not checked yetcites Klein, 2002
- Not checked yetcites Haass and Selkoe, 2007
boosted- 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.
In the paper
“Apoe is one of the most highly induced genes in mouse microglia in response to neurodegenerative stimuli (Deczkowska et al., 2018).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
What the sources say
- Not checked yetcites Deczkowska et al., 2018
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.
None of the sources cited for this claim have been checked yet.
In the paper
“NfL measured in the CSF or plasma has recently emerged as a potential biomarker of neurodegeneration in human patients and in mouse disease models (Bacioglu et al., 2016; Khalil et al., 2018).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
What the sources say
- Not checked yetcites Bacioglu et al., 2016
- Not checked yetcites Khalil et al., 2018
hedged- 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
“Although we were blinded to Trem2 genotype, there was an obvious difference in plaque appearance between PS2APP;Trem2wt and PS2APP;Trem2ko brains, with X-34+ structures in PS2APP;Trem2ko brains looking more splayed and less compact (Fig. 4A), similar to descriptions of Trem2-dependent plaque alterations in other β-amyloid models (Wang et al., 2016; Yuan et al., 2016).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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
“Alternatively, the increased abundance of fibrillar Aβ oligomers in the TBS-soluble fraction could result from reduced incorporation into highly condensed plaques in brains with Trem2-deficient microglia.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Reduced plaque consolidation, elevated neurotoxic Aβ species, and ApoE-laden microglia in Trem2-deficient brains
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.
None of the sources cited for this claim have been checked yet.
In the paper
“elevated PET signal for ligands of the “neuroinflammation marker” TSPO have predicted better cognitive measures and slower AD progression in mice with β-amyloid pathology and human patients, respectively (Hamelin et al., 2016; Focke et al., 2019).”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Discussion
What the sources say
- Not checked yetcites Hamelin et al., 2016
- Not checked yetcites Focke et al., 2019
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.
None of the sources cited for this claim have been checked yet.
In the paper
“another feature of neuronal pathology observed in AD tissues and β-amyloid mouse models, reduced synaptic density, particularly near plaque (Spires and Hyman, 2004; Tsai et al., 2004; Spires et al., 2005)”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Results > Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2ko mice
What the sources say
- Not checked yetcites Spires and Hyman, 2004
- Not checked yetcites Tsai et al., 2004
- Not checked yetcites Spires et al., 2005
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.
Probably not a substantial claim.
In the paper
“Together with a recent similar report (Parhizkar et al., 2019), these results suggest that Trem2-dependent microglial activity may both restrain the formation/seeding of plaques at an early stage of pathology, conceivably through uptake and degradation of soluble Aβ species, but also enhance the sequestration of Aβ into existing plaque structures, particularly at later stages of pathology.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Discussion
What the sources say
- Not checked yetcites Parhizkar et al., 2019
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Evidence in humans and mice supports the mechanistic model that β-amyloid pathology accelerates the accumulation of tau pathology or enhances its spreading (Pooler et al., 2015; He et al., 2018; Jack et al., 2018; Jacobs et al., 2018)”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > Discussion
What the sources say
- Not checked yetcites Pooler et al., 2015
- Not checked yetcites He et al., 2018
- Not checked yetcites Jack et al., 2018
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.
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
“The reduction of this plaque accumulation activity in PS2APP;Trem2ko brains may underlie the elevated levels of fibrillar oligomeric Aβ we detected in the soluble fraction, which may in turn be a source of increased neuronal injury in these animals.”
§ Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model > 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.
It may state two separate claims as one.
The paper relies on this without support.
The effects of Trem2 deletion in PS2APP mice are mediated specifically by microglial Trem2 rather than by other Trem2-expressing myeloid cells or non-myeloid cells.
“TREM2 is an Alzheimer's disease (AD) risk gene expressed in microglia.”
The paper relies on this without support.
The Trem2tm1(KOMP)Vlcg allele completely abolishes Trem2 function in PS2APP;Trem2ko mice.
“The Trem2tm1(KOMP)Vlcg null allele (C57BL/6N background) was crossed into the PS2APP model (C57BL/6J background).”
The paper relies on this without support.
Amber core amyloid staining represents a mature form of highly condensed plaque.
“At this age, the Campbell-Switzer stain also revealed a distinctive pattern of “amber core” amyloid staining in PS2APP brains (Fig. 3C), thought to represent a mature form of highly condensed plaque.”
The paper relies on this without support.
Cognitive decline correlates better with tau pathology and synapse loss than with brain amyloid detection.
“helps explain why cognitive decline correlates better with tau pathology and synapse loss than with brain amyloid detection.”
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 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 progression is better correlated with tau pathology, neuronal degeneration, Aβ spreading and synapse loss, rather than Aβ detection alone [222]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [222]
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
“which may be a result of reduced oligomeric Aβ compaction as described previously in another amyloidogenic mouse model. 62”
From PLCG2 modulates TREM2 expression and signaling in response to Alzheimer's disease pathology (2025) · cites this paper as [62]
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
“More recently, this dichotomy has been elegantly demonstrated in multiple models of Trem2 and Tyrobp [49–51, 55–59].”
From Deletion of Abi3/Gngt2 influences age-progressive amyloid β and tau pathologies in distinctive ways (2022) · cites this paper as [57]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“A similar interpretation could be developed from the studies of Trem2 deficiency, as differences were dependent on early versus later disease stages.50,51,57,58”
From Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer's disease (2023) · cites this paper as [57]
The cited source says what the claim attributes to it.
In the citing paper
“These studies have led to the notion that microglia can have differential effects on AD pathology depending on the disease stage.”
From The effect of Abi3 locus deletion on the progression of Alzheimer’s disease-related pathologies (2023) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“Earlier studies on other microglial AD risk genes reported opposing effects on AD-related pathologies using various animal models at different ages (8–14).”
From The effect of Abi3 locus deletion on the progression of Alzheimer’s disease-related pathologies (2023) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“Functional studies demonstrated that deletion of Trem2 altered amyloid pathology in opposite directions depending on the stage of the disease (20–23), but overexpression of TREM2 reduced the pathology in transgenic mouse models of amyloidosis (24).”
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 [23]
The cited source says what the claim attributes to it.
In the citing paper
“Conflicting results have been reported regarding amyloid plaque deposition and the effect of TREM2 loss [7,8,9,10,11], suggesting that the effect of TREM2 on Ab deposition may be dependent on age, sex, and the model utilized.”
From TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo (2023) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“Indeed, manipulation of expression of Trem2, Tyrobp, Cx3cl1/Cx3cr1, IL1β, and IFN-γ have all been shown to have opposing effects on amyloid and tau pathologies [49–51, 55–65].”
From Deletion of Abi3/Gngt2 influences age-progressive amyloid β and tau pathologies in distinctive ways (2022) · cites this paper as [57]
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 [98]
Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · cited 1×
“Normalization was based on the nRPKM method, which is proportional to size factor normalization of DESeq (Love et al., 2014).”
Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226 · cited 1×
“Moreover, many have proposed that chronic microglial activation is a key damaging agent that contributes to the neurotoxic environment in AD (Heneka et al., 2015; Park et al., 2018).”
Backgroundvoom: precision weights unlock linear model analysis tools for RNA-seq read counts
Law, C. W., Chen, Y., Shi, W., & Smyth, G. K. (2014) · Genome Biology · doi:10.1186/gb-2014-15-2-r29 · Cited by 6,155 · cited 1×
“Differential expression was performed using voom limma (Law et al., 2014).”
MethodA 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 · cited 12×
“The entirety of these changes is approximately equivalent to the so-called DAM (Keren-Shaul et al., 2017) or MgND (Krasemann et al.”
BackgroundMethodResultInfluentialSoluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · cited 2×
“Axonal dystrophy, dendritic spine loss, and CSF NfL detection are exacerbated in PS2APP;Trem2 ko mice The elevated A 42:A 40 ratio and fibrillar A oligomers in PS2APP;Trem2 ko brains would seem to be detrimental for neuronal health since A 42 oligomers are commonly understood to be the more toxic form of A (Klein, 200…”
BackgroundComplement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343 · cited 2×
“…underscored that the Trem2-dependent microglial activation around plaque is protective for neurons and is distinct from microglia-mediated, complement-mediated activities that contribute to synapse loss in -amyloid models (Fonseca et al., 2004; Hong et al., 2016; Shi et al., 2017; Wu et al., 2019).”
BackgroundMi, H., Muruganujan, A., Ebert, D., Huang, X., & Thomas, P. D. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky1038 · Cited by 3,030 · cited 2×
“1 (Mi et al., 2019) at the website (http:// pantherdb.”
MethodInfluentialTREM2 Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020 · cited 2×
“Since the discovery of TREM2 (triggering receptor expressed on myeloid cells 2) variants as genetic risk factors for Alzheimer’s disease (AD) (Guerreiro et al., 2013; Jonsson et al., 2013), TREM2 biology has become a focal point in research efforts to better understand how the innate immune system impacts AD and other…”
BackgroundKrasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O’Loughlin, E., Xu, Y., Fanek, Z., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.08.008 · Cited by 2,979 · cited 6×
“Although two groups have reported reductions in microglial Apoe expression in the APPPS1 model when Trem2 is deleted (Krasemann et al., 2017; Parhizkar et al., 2019), this does not appear to be a typical feature of Trem2 deficiency in -amyloidosis models since previous analyses in the 5xFAD model…”
BackgroundMethodResultInfluentialVariant of TREM2 Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558 · cited 2×
“Since the discovery of TREM2 (triggering receptor expressed on myeloid cells 2) variants as genetic risk factors for Alzheimer’s disease (AD) (Guerreiro et al., 2013; Jonsson et al., 2013), TREM2 biology has become a focal point in research efforts to better understand how the innate immune system impacts AD and other…”
Background
Research works printed but not linked: 1
- Campbell, 1987, Alzheimer's plaques and tangles: a controlled and enhanced silver staining method, Soc Neuroscience Abstr, 13, 678
Cited by
Sorted by citations
The Physiology, Pathology, and Potential Therapeutic Applications of the TREM2 Signaling Pathway
Deczkowska, A., Weiner, A., & Amit, I. (2020) · Cell · doi:10.1016/j.cell.2020.05.003 · Cited by 648
Microglia regulation of synaptic plasticity and learning and memory
Zhou, M., Cornell, J., Salinas, S., & Huang, H.-Y. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.322423 · Cited by 548
Dejanovic, B., Wu, T., Tsai, M.-C., Graykowski, D., Gandham, V. D., Rose, C. M., Bakalarski, C. E., Ngu, H., Wang, Y., Pandey, S., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00281-1 · Cited by 341
Self-citationTrem2 restrains the enhancement of tau accumulation and neurodegeneration by β-amyloid pathology
Lee, S.-H., Meilandt, W. J., Xie, L., Gandham, V. D., Ngu, H., Barck, K. H., Rezzonico, M. G., Imperio, J., Lalehzadeh, G., Huntley, M. A., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.02.010 · Cited by 300
Self-citationSengupta, U., & Kayed, R. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102270 · Cited by 314
Metadata
- Authors
- Meilandt, W. J., Ngu, H., Gogineni, A., Lalehzadeh, G., Lee, S.-H., Srinivasan, K., Imperio, J., Wu, T., Weber, M., Kruse, A. J., Stark, K. L., Chan, P., Kwong, M., Modrusan, Z., Friedman, B. A., Elstrott, J., Foreman, O., Easton, A., Sheng, M., & Hansen, D. V.
- Affiliations
- Genentech (US)
- Corresponding author
- Meilandt, William J.
- Hansen, David V.
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2020-01-24
- Volume
- 40
- Issue
- 9
- Pages
- 1956-1974
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC7046459
- OpenAlex
- W3003126983
- Semantic Scholar
- 24b2107485715864dc70c72f73ce957a07b3f7a9
- Cited by
- 210
- References
- 98
- Citations by year
- 2026: 16 · 2025: 30 · 2024: 44 · 2023: 48 · 2022: 33 · 2021: 25 · 2020: 14
- FWCI
- 18.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- TREM2, Alzheimer's disease, amyloid plaques, amyloid-beta 42/40 ratio, axonal dystrophy, dendritic spine loss, neuritic dystrophy, microglial activation, soluble amyloid-beta oligomers, neurofilament light chain, apolipoprotein E, Wnt signaling, sex differences
- MeSH terms
- Trefoil Factor-1, Alzheimer Disease, Animals, Axons, Female, Male, Membrane Glycoproteins, Mice, Inbred C57BL, Peptide Fragments, Receptors, Immunologic, Amyloid beta-Peptides, Neurites, Amyloid beta-Protein Precursor, Neurofilament Proteins, Microglia, Mice, Knockout, Dendritic Spines, Mice, Plaque, Amyloid
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 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
