The DOI matches its Crossref record; 224 of the 225 references it cites were found in a registry or an index; 38 of the 275 sources its claims cite were checked for support.
Microglial signatures and their role in health and disease
Open accessAbstract
Microglia are the primary innate immune cells in the CNS. In the healthy brain, they exhibit a unique molecular homeostatic ‘signature’, consisting of a specific transcriptional profile and surface protein expression pattern, which differs from that of tissue macrophages. In recent years, there have been a number of important advances in our understanding of the molecular signatures of homeostatic microglia and disease-associated microglia that have provided insight into how these cells are regulated in health and disease and how they contribute to the maintenance of the neural environment. Technological advances have allowed the molecular ‘signatures’ of microglia to be characterized, providing insight into their roles in CNS function. Weiner and Butovsky discuss the plasticity of these signatures in health and disease and consider the mechanisms underlying their establishment, maintenance and regulation.
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Claims the paper makes
140 Not checked yet · 22 Own interpretation · 12 Partly supported · 4 Supported · 1 Not supported · 1 No basis given · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Thus, most of the microglial population is renewed several times over the course of a lifetime15.”
§ Microglial signatures and their role in health and disease > Abstract
What the sources say
- Supportedcites [15] Reu, P. et al. The lifespan and turnover of microglia in the human brain. Cell Rep. 20, 779–784 (2017). source
The Results report that most microglia in the healthy human cortex are replaced at a median rate of 28% per year. That rate supports repeated population renewal over a human lifetime; the Discussion also predicts nearly complete renewal during an individual's lifespan. The paper frames the lifetime conclusion as a prediction, rather than a direct observation. (LLM, conf=0.90)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Microglia play a crucial role in synaptic and axonal pruning during development by phagocytizing inappropriate synaptic connections and axons, thereby shaping neural circuits in the developing brain41,88–90.”
§ Microglial signatures and their role in health and disease > Microglial physiological functions > Synaptic plasticity and synaptogenesis
What the sources say
- Not checked yetcites [41] Perry, V. H., Hume, D. A. & Gordon, S. Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience 15, 313–326 (1985). source
- Partly supportedcites [88] Bialas, A. R. & Stevens, B. TGF-beta signaling regulates neuronal C1q expression and developmental synaptic refinement. Nat. Neurosci. 16, 1773–1782 (2013). sourceExperimental — accuracy not yet measured
The Results section reports microglial phagocytosis of retinal ganglion cell terminals during developmental synapse elimination, and the Discussion links this pruning to circuit refinement. The copy does not establish the separate claim that microglia phagocytize axons during axonal pruning. Page numbers were not available in the indexed passages. (LLM, conf=0.83)
- Partly supportedcites [89] Schafer, D. P. & Stevens, B. Phagocytic glial cells: sculpting synaptic circuits in the developing nervous system. Curr. Opin. Neurobiol. 23, 1034–1040 (2013). sourceExperimental — accuracy not yet measured
The ‘Pruning of local synaptic circuits’ section reports that microglia engulf presynaptic inputs during postnatal pruning, supporting their role in shaping developing circuits. But the ‘Axonal Pruning in the CNS’ section says little is known about glia’s role in large-scale axonal pruning in mammals; its stronger evidence for engulfment of axons concerns Drosophila glia, not specifically microglia. The claim therefore overstates the evidence for microglial axonal pruning in the developing brain. (LLM, conf=0.88)
- Partly supportedcites [90] Paolicelli, R. C. et al. Synaptic pruning by microglia is necessary for normal brain development. Science 333, 1456–1458 (2011). sourceExperimental — accuracy not yet measured
The Abstract reports that microglia engulf synaptic material during postnatal development in mice, and the conclusion links impaired synaptic pruning to delayed circuit maturation. The paper does not show microglia engulfing or pruning axons; its discussion mentions developmental axon pruning only in connection with complement-cascade components. (LLM, conf=0.88)
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 cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The disease-associated microglial transcriptional phenotype in EAE also contributes to the inflammatory cascade by activating astrocytes150.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Multiple sclerosis
What the sources say
- Partly supportedcites [150] Liddelow, S. A. et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481–487 (2017).This study shows that classically activated neuroinflammatory microglia induce toxic astrocytes, which contribute to the death of neurons and oligodendrocytes in neurodegenerative disorders. sourceExperimental — accuracy not yet measured
Section 2 reports that LPS-activated microglia, unlike resting microglia, induce A1 reactive astrocytes through IL-1α, TNFα, and C1q. The paper also identifies A1-like astrocytes in human multiple sclerosis lesions (Extended Data, Fig. 13), but these passages do not establish that the disease-associated microglial transcriptional phenotype in EAE activates astrocytes or contributes to its inflammatory cascade. (LLM, conf=0.88)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This phenotype was not observed in microglia in non-plaque areas, suggesting that the neuroinflammation associated with AD predominantly occurs in plaque-associated microglia.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Alzheimer disease
What the sources say
- Supportedcites [52] Krasemann, S. et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581 (2017).This study identifies a major microglial neurodegenerative phenotype in rodent and humans regulated by TREM2–ApoE signalling. source
In the Results section on MGnD microglia and neuritic plaques (page unavailable), the paper identifies non-plaque-associated microglia as a distinct subset and reports that only the plaque-associated Clec7a+ subset acquired the MGnD signature, which includes upregulated inflammatory molecules. Its observations in human AD also place the phenotype switch near neuritic plaques. The sentence’s broader suggestion about where AD neuroinflammation predominantly occurs is the citing authors’ inference. (LLM, conf=0.88)
- Partly supportedcites [111] Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290 (2017).This study utilizes unbiased single-cell RNA-sequencing analysis to define DAM microglia. sourceExperimental — accuracy not yet measured
The Results (page unavailable) locate disease-associated microglia predominantly near Aβ plaques, but report some plaque-ingesting microglia even in regions with low plaque density. The Discussion (page unavailable) describes these cells as protective and associated with phagocytosis, not as a proinflammatory phenotype; the paper does not establish that AD neuroinflammation predominantly occurs in plaque-associated microglia. (LLM, conf=0.86)
- Partly supportedcites [139] Kamphuis, W., Kooijman, L., Schetters, S., Orre, M. & Hol, E. M. Transcriptional profiling of CD11c-positive microglia accumulating around amyloid plaques in a mouse model for Alzheimer’s disease. Biochim. Biophys. Acta 1862, 1847–1860 (2016). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) describes pro-inflammatory proteins in microglia surrounding amyloid plaques, and the Conclusions identify activated microglia associated with plaques in the APP/PS1 mouse model. The paper does not establish that a pro-inflammatory phenotype is absent from microglia in non-plaque areas; its comparison is primarily between two plaque-associated microglial populations. (LLM, conf=0.83)
- Not checked yetcites [140] Yin, Z. et al. Immune hyperreactivity of Aß plaque-associated microglia in Alzheimer’s disease. Neurobiol. Aging 55, 115–122 (2017). source
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The upregulated genes in Aβ-plaque-associated microglia, also known as disease-associated microglia (‘DAM microglia’), included Axl, Apoe, Clec7a, Itgax, Lgals3 and Cst7”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Alzheimer disease
What the sources say
- Partly supportedcites [52] Krasemann, S. et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581 (2017).This study identifies a major microglial neurodegenerative phenotype in rodent and humans regulated by TREM2–ApoE signalling. sourceExperimental — accuracy not yet measured
The Results section on plaque-associated MGnD microglia identifies Aβ-plaque-associated cells in APP-PS1 mice and lists Axl, Apoe, Clec7a and Itgax as upregulated. Another Results section describes Lgals3 as disease-associated, but the plaque-associated gene list does not include it; searches for Cst7 found no supporting passage. The paper calls this phenotype MGnD, not DAM. Page numbers were not available in our copy. (LLM, conf=0.87)
- Partly supportedcites [111] Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290 (2017).This study utilizes unbiased single-cell RNA-sequencing analysis to define DAM microglia. sourceExperimental — accuracy not yet measured
The Results identify DAM near Aβ plaques and report increased Apoe and Cst7 expression during the transition to DAM. They also identify Itgax and Clec7a as potential DAM markers. Our copy does not substantiate Axl or Lgals3 as upregulated DAM genes (searched both names). (LLM, conf=0.85)
- Partly supportedcites [139] Kamphuis, W., Kooijman, L., Schetters, S., Orre, M. & Hol, E. M. Transcriptional profiling of CD11c-positive microglia accumulating around amyloid plaques in a mouse model for Alzheimer’s disease. Biochim. Biophys. Acta 1862, 1847–1860 (2016). sourceExperimental — accuracy not yet measured
Section 3.4 identifies Apoe, Axl, Clec7a, Itgax and Lgals3 as upregulated in the APP/PS1 CD11c microglia and separately lists Cst7 among genes with increased expression. The paper describes these cells as plaque-associated, but our copy does not identify them as “disease-associated microglia” or “DAM microglia.” (LLM, conf=0.86)
- Not checked yetcites [140] Yin, Z. et al. Immune hyperreactivity of Aß plaque-associated microglia in Alzheimer’s disease. Neurobiol. Aging 55, 115–122 (2017). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Microglial activation in human PD has been demonstrated by positron emission tomography161”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Parkinson disease
What the sources say
- Partly supportedcites [161] Koshimori, Y. et al. Imaging striatal microglial activation in patients with Parkinson’s disease. PLOS ONE 10, e0138721 (2015). sourceExperimental — accuracy not yet measured
The Introduction reports that some PET studies found elevated TSPO binding in patients with Parkinson’s disease, consistent with imaging evidence of microglial activation. It also calls those findings inconclusive, and the Discussion and Conclusions report no significant disease effect on striatal TSPO expression in this study. The unqualified claim that PET has demonstrated activation overstates the evidence this paper presents. (LLM, conf=0.86)
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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Furthermore, an elevation in the levels of soluble TREM2 in the cerebrospinal fluid in AD is coincident with markers of neural damage and the onset of clinical dementia170.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Partly supportedcites [170] Piccio, L. et al. Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status. Acta Neuropathol. 131, 925–933 (2016). sourceExperimental — accuracy not yet measured
The Results report higher CSF sTREM2 in AD cases than in cognitively normal controls and a correlation with CSF tau and p-tau, supporting the association with markers of neural damage. The Study population section says most AD cases had very mild or mild dementia, but the paper does not establish when sTREM2 rises relative to the onset of clinical dementia. (LLM, conf=0.83)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“During the progressive stages of MS, microglia have been shown to accumulate iron151,152.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Multiple sclerosis
What the sources say
- Supportedcites [151] Hametner, S. et al. Iron and neurodegeneration in the multiple sclerosis brain. Ann. Neurol. 74, 848–861 (2013). source
The Results section reports high iron loads within microglia at MS lesion edges. The Sample Characterization section confirms that the study included patients with secondary and primary progressive MS, supporting the claim in the progressive-stage context. (LLM, conf=0.90)
- Supportedcites [152] Dal-Bianco, A. et al. Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging. Acta Neuropathol. 133, 25–42 (2017). source
The Conclusions report that, in patients with relapsing or progressive MS, iron accumulates in microglia/macrophages at the edges of slowly expanding lesions. The Results (Post-mortem study) also document iron-laden microglia/macrophages at those lesion edges. (LLM, conf=0.91)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Indeed, TREM2 is an important microglial molecule25,27,28 thought to be involved in the regulation of microglial signatures in disease1,58.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Could not verifycites [25] Butovsky, O. et al. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat. Neurosci. 17, 131–143 (2014).This study identifies the molecular and functional signature of homeostatic microglia, which depends on TGFβ signalling. sourceExperimental — accuracy not yet measured
The Results and Abstract identify a microglial molecular signature and attribute its regulation to TGF-β. Searches for TREM2 and for regulation of disease-associated microglial signatures found no passage in our copy that addresses a role for TREM2; the cited paper therefore cannot verify the specific claim. (LLM, conf=0.75)
- Supportedcites [27] Hickman, S. E. et al. The microglial sensome revealed by direct RNA sequencing. Nat. Neurosci. 16, 1896–1905 (2013). source
The source supports the part of the citing sentence that identifies TREM2 as an important microglial molecule. In the Results (Identification of the microglial Sensome by DRS), it lists TREM2 among sensome proteins associated with DAP12; the Discussion also identifies TREM2 as a member of the microglial sensome and an Alzheimer’s disease risk factor. The separate claim about regulating disease-associated microglial signatures is attached to other citations in the sentence. (LLM, conf=0.90)
- Partly supportedcites [28] Chiu, I. M. et al. A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model. Cell Rep. 4, 385–401 (2013). sourceExperimental — accuracy not yet measured
The Discussion identifies TREM2 as a microglial receptor upregulated during disease progression, and the Results link TREM2 mutations to microglial dysfunction. Neither passage shows that TREM2 regulates microglial gene-expression signatures; the paper reports its expression as part of a disease-associated signature. (LLM, conf=0.83)
- Partly supportedcites [1] Colonna, M. & Butovsky, O. Microglia function in the central nervous system during health and neurodegeneration. Annu. Rev. Immunol. 35, 441–468 (2017). sourceExperimental — accuracy not yet measured
The section “Regulatory Immune Receptors in Alzheimer Disease” describes TREM2 as a microglial signaling receptor and reports that TREM2 deficiency reduces microglial clustering around amyloid plaques in mouse models. This supports a role in disease-related microglial responses, but the review does not say that TREM2 regulates microglial gene-expression signatures in disease. (LLM, conf=0.83)
- Not checked yetcites [58] Colonna, M. & Wang, Y. TREM2 variants: new keys to decipher Alzheimer disease pathogenesis. Nat. Rev. Neurosci. 17, 201–207 (2016). source
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.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“For example, soluble TREM2 has been shown to increase with time with the development of AD211.”
§ Microglial signatures and their role in health and disease > Therapeutic targeting of microglia
What the sources say
- Partly supportedcites [211] Brendel, M. et al. Increase of TREM2 during aging of an Alzheimer’s disease mouse model is paralleled by microglial activation and amyloidosis. Front. Aging Neurosci. 9, 8 (2017). sourceExperimental — accuracy not yet measured
The Results report a progressive age-dependent increase in brain sTREM2 in an Alzheimer’s disease mouse model. The Discussion distinguishes that finding from human AD: CSF sTREM2 rises around early stages but falls later in the disease course. The claim omits the mouse-model and disease-stage limits. (LLM, conf=0.88)
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.
- Partly supported
- It may state two separate claims as one. 81
- The quote only partly states this claim. 2
- Probably not a substantial claim. 18
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“microglia express lower levels of receptor-type tyrosine-protein phosphatase C (PTPRC; also known as CD45) than monocytes, allowing these two cell types to be discriminated, whereas the expression of scavenger receptor cysteine-rich type 1 protein M130 (CD163) by microglia enables their distinction from perivascular macrophages35,44–47.”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Microglial surface protein signature
What the sources say
- Disputedcites [35] Bennett, M. L. et al. New tools for studying microglia in the mouse and human CNS. Proc. Natl Acad. Sci. USA 113, E1738–E1746 (2016). sourceExperimental — accuracy not yet measured
The introduction describes CD45 hi/lo expression as a way to distinguish microglia from other CNS cells, supporting the CD45 portion. But the section on Tmem119 mRNA identifies the perivascular cells as Cd163-positive and Tmem119 as the microglial marker—the reverse of the claim that microglial CD163 expression makes the distinction. Page numbers were not available in our copy. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
- Not checked yetcites [44] Vainchtein, I. D. et al. In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed. Glia 62, 1724–1735 (2014). source
- Not checked yetcites [45] van den Berg, T. K., Puklavec, M. J., Barclay, A. N. & Dijkstra, C. D. Monoclonal antibodies against rat leukocyte surface antigens. Immunol. Rev. 184, 109–116 (2001). source
- Disputedcites [46] Kim, W. K. et al. CD163 identifies perivascular macrophages in normal and viral encephalitic brains and potential precursors to perivascular macrophages in blood. Am. J. Pathol. 168, 822–834 (2006). sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) says the opposite of the claim's CD163 attribution: perivascular macrophages express CD163, while parenchymal microglia are largely CD163-negative. Our copy does not establish that microglia have lower CD45 levels than monocytes; the CD45 mention found is a reference title stating only that microglia express CD45. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
- Not checked yetcites [47] Sousa, C., Biber, K. & Michelucci, A. Cellular and molecular characterization of microglia: a unique immune cell population. Front. Immunol. 8, 198 (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.
It may state two separate claims as one.
- Disputed
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Sal-like protein 1 (SALL1), regulates cortical neurogenesis and is expressed in human and mouse microglia25.”
- Also stated in: § Mechanisms of homeostatic microglia regulation · plain
“Mutations in SALL1 result in neural or behavioural abnormalities in humans85 and abnormal microglial morphology and downregulation of the microglial homeostatic signature in mice86”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Mechanisms of homeostatic microglia regulation
What the sources say
- Partly supportedcites [25] Butovsky, O. et al. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat. Neurosci. 17, 131–143 (2014).This study identifies the molecular and functional signature of homeostatic microglia, which depends on TGFβ signalling. sourceExperimental — accuracy not yet measured
The Results section ('Identification of a unique microglial signature'; page unavailable) identifies Sall1 among genes expressed in mouse microglia, but its human-microglia results do not include SALL1. The paper does not establish that SALL1 regulates cortical neurogenesis or report effects of SALL1 mutations. Its findings on abnormal microglial morphology and reduced Sall1 expression concern mice deficient in CNS TGF-β1, not mice with SALL1 mutations. (LLM, conf=0.87)
- Partly supportedcites [85] Harrison, S. J., Nishinakamura, R., Jones, K. R. & Monaghan, A. P. Sall1 regulates cortical neurogenesis and laminar fate specification in mice: implications for neural abnormalities in Townes-Brocks syndrome. Dis. Model. Mech. 5, 351–365 (2012). sourceExperimental — accuracy not yet measured
The Abstract reports that Sall1 regulates cortical neurogenesis in mice and that SALL1 mutations are associated with Townes–Brocks syndrome, in which some patients have neural or behavioral abnormalities. The Results section identifies possible glial cells in the mouse cortical wall but does not identify them as microglia. Our copy does not establish SALL1 expression in human and mouse microglia or report abnormal microglial morphology or downregulation of a homeostatic signature. (LLM, conf=0.88)
- Not checked yetcites [86] Buttgereit, A. et al. Sall1 is a transcriptional regulator defining microglia identity and function. Nat. Immunol. 17, 1397–1406 (2016). source
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.
- Also stated in: § Mechanisms of homeostatic microglia regulation · plain
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Tau, presenilin 2 and apolipoprotein E (ApoE) pathways were found to be activated in microglia in the SOD1 mouse, with Apoe being one of the transcripts that was the most significantly induced during disease progression.”
- Also stated in: § Amyotrophic lateral sclerosis · plain
“this study also revealed loss of the homeostatic microglial signature described above as early as 2 months before measurable disease onset in the SOD1 mouse.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Amyotrophic lateral sclerosis
What the sources say
- Supportedcites [28] Chiu, I. M. et al. A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model. Cell Rep. 4, 385–401 (2013). source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [84] Butovsky, O. et al. Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1 mice. Ann. Neurol. 77, 75–99 (2015).This study validates miR-155 as a therapeutic target to modulate microglia in a mouse model and in human ALS. sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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.
- Also stated in: § Amyotrophic lateral sclerosis · plain
Every source the paper cites for this claim was checked and supports it.
In the paper
“TREM2 is a receptor that detects damage-associated lipids, allowing microglia to sense Aβ accumulation, and its loss has been shown to augment Aβ accumulation in a mouse model of AD166.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Supportedcites [166] Wang, Y. et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model. Cell 160, 1061–1071 (2015).This study demonstrates that microglial TREM2 is a sensor for lipids associated with fibrillar Aβ and its loss affects microglia and augments Aβ accumulation. source
The Abstract reports that TREM2 senses damage-associated lipids associated with Aβ and that TREM2 deficiency increases Aβ accumulation in the 5XFAD mouse model. The Discussion clarifies that TREM2 senses lipids rather than binding Aβ directly, consistent with the claim. (LLM, conf=0.95)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Methods to image microglia exist and are being used to test the effect of treatments on microglia205–210.”
§ Microglial signatures and their role in health and disease > Therapeutic targeting of microglia
What the sources say
- Partly supportedcites [205] Nimmerjahn, A. Two-photon imaging of microglia in the mouse cortex in vivo. Cold Spring Harb. Protoc. https://doi.org/10.1101/pdb.prot069294 (2012). sourceExperimental — accuracy not yet measured
The Discussion (page not provided) says several techniques enable minimally invasive imaging of microglia, and the paper describes a two-photon imaging protocol. Although the References include a study of microglial response after antibody administration, this paper does not itself say that its imaging method is being used to test treatment effects on microglia. (LLM, conf=0.83)
- Supportedcites [206] Dupont, A. C. et al. Translocator protein-18 kDa (TSPO) positron emission tomography (PET) imaging and its clinical impact in neurodegenerative diseases. Int. J. Mol. Sci. https://doi.org/10.3390/ijms18040785 (2017). source
The Multiple Sclerosis section reports that microglia PET imaging with 11C-PK11195 was used to assess the effect of a disease-modifying drug, glatiramer acetate. It describes a statistically decreased imaging signal after one year of treatment, supporting both parts of the attributed claim. (LLM, conf=0.93)
- Partly supportedcites [207] Ghadery, C. et al. Microglial activation in Parkinson’s disease using [18F]-FEPPA. J. Neuroinflamm. 14, 8 (2017). sourceExperimental — accuracy not yet measured
The Background and Discussion describe PET radioligands used to image neuroinflammation and microglial activation. The Discussion reports no correlation between anti-parkinsonian medication and the imaging measure, but does not describe using imaging to test a treatment’s effect on microglia. That part of the claim is unsupported by this paper. (LLM, conf=0.86)
- Supportedcites [208] Cerami, C., Iaccarino, L. & Perani, D. Molecular imaging of neuroinflammation in neurodegenerative dementias: the role of in vivo PET imaging. Int. J. Mol. Sci. FF (2017). source
The Conclusions (section 5; page unavailable) identify TSPO-PET as a tool for detecting activated microglia and report that studies have used it to assess brain inflammation before and after anti-inflammatory treatment. This supports both the existence of imaging methods and their use to test treatment effects. (LLM, conf=0.94)
- Partly supportedcites [209] Hamelin, L. et al. Early and protective microglial activation in Alzheimer’s disease: a prospective study using 18F-DPA-714 PET imaging. Brain 139, 1252–1264 (2016). sourceExperimental — accuracy not yet measured
The Discussion (page not provided) identifies ¹⁸F-DPA-714 PET as a potential tool for assessing neuroinflammation, supporting the existence of an imaging method. It discusses interest in microglia-targeted therapies but does not report using imaging to test a treatment’s effect on microglia. (LLM, conf=0.85)
- Partly supportedcites [210] Politis, M., Su, P. & Piccini, P. Imaging of microglia in patients with neurodegenerative disorders. Front. Pharmacol. 3, 96 (2012). sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) describes PET with TSPO radioligands as a way to image activated microglia, supporting the existence of imaging methods. The Conclusion (page unavailable) says PET detection could offer opportunities for pharmacological interventions, but does not say imaging is already being used to test treatments’ effects on microglia. (LLM, conf=0.84)
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In the paper
“Microglia exist in resting or activated states depending on the inflammatory milieu, which differs in the healthy CNS and in various disease states19–22.”
§ Microglial signatures and their role in health and disease > Abstract
What the sources say
- Not checked yetcites [19] Ransohoff, R. M. & Cardona, A. E. The myeloid cells of the central nervous system parenchyma. Nature 468, 253–262 (2010). source
- Not checked yetcites [20] Kettenmann, H., Hanisch, U. K., Noda, M. & Verkhratsky, A. Physiology of microglia. Physiol. Rev. 91, 461–553 (2011). source
- Not checked yetcites [21] Hanisch, U. K. & Kettenmann, H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10, 1387–1394 (2007). source
- Not checked yetcites [22] Hanisch, U. K. Functional diversity of microglia - how heterogeneous are they to begin with? Front. Cell. Neurosci. 7, 65 (2013). source
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“a genome-wide analysis of gene expression in microglia from different brain regions across the adult lifespan of the mouse was performed found that there are region-specific transcriptional profiles and age-dependent regional variability in gene expression59.”
- Also stated in: § Microglial heterogeneity and plasticity · hedged
“The findings further suggested that cerebellar and hippocampal microglia exist in a more ‘immune-vigilant’ state than microglia in forebrain regions.”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Microglial heterogeneity and plasticity
What the sources say
- Not checked yetcites [59] Grabert, K. et al. Microglial brain region-dependent diversity and selective regional sensitivities to aging. Nat. Neurosci. 19, 504–516 (2016).This study describes the age-dependent and region-dependent transcriptional heterogeneity of microglia. source
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In the paper
“during inflammation, microglia change from a ‘bushy’ shape with extended processes to become amoeboid and produce inflammatory factors62,63.”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Microglial heterogeneity and plasticity
What the sources say
- Not checked yetcites [62] Ladeby, R. et al. Microglial cell population dynamics in the injured adult central nervous system. Brain Res. Rev. 48, 196–206 (2005). source
- Not checked yetcites [63] Ziebell, J. M., Adelson, P. D. & Lifshitz, J. Microglia: dismantling and rebuilding circuits after acute neurological injury. Metab. Brain Dis. 30, 393–400 (2015). source
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“this method of distinguishing between cell types relies on relative surface marker expression as assessed by flow cytometry, which can have some limitations. For example, CD45 surface expression is known to be upregulated on microglia associated with amyloid-β (Aβ) plaques in the APP/PS1 mouse model of Alzheimer disease (AD)52.”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Microglial surface protein signature
What the sources say
- Not checked yetcites [52] Krasemann, S. et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581 (2017).This study identifies a major microglial neurodegenerative phenotype in rodent and humans regulated by TREM2–ApoE signalling. source
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In the paper
“sialoadhesin (SIGLEC1; also known as CD169) is a marker for mature dendritic cells and macrophages in both mice and humans48 and has been proposed as a marker for invading monocyte-derived macrophages in the CNS as it is not expressed in microglia in health or disease49–52.”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Microglial surface protein signature
What the sources say
- Not checked yetcites [48] Davies, L. C., Jenkins, S. J., Allen, J. E. & Taylor, P. R. Tissue-resident macrophages. Nat. Immunol. 14, 986–995 (2013). source
- Not checked yetcites [49] Butovsky, O. et al. Modulating inflammatory monocytes with a unique microRNA gene signature ameliorates murine ALS. J. Clin. Invest. 122, 3063–3087 (2012).This study shows the relevance of innate inflammation for ALS pathogenesis and identifies miR-155 as a potential therapeutic target. source
- Not checked yetcites [50] Gao, L. et al. Infiltration of circulating myeloid cells through CD95L contributes to neurodegeneration in mice. J. Exp. Med. 212, 469–480 (2015). source
- Not checked yetcites [51] Zondler, L. et al. Peripheral monocytes are functionally altered and invade the CNS in ALS patients. Acta Neuropathol. 132, 391–411 (2016). source
- Not checked yetcites [52] Krasemann, S. et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581 (2017).This study identifies a major microglial neurodegenerative phenotype in rodent and humans regulated by TREM2–ApoE signalling. source
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In the paper
“Human microglia turn over at a yearly median rate of 28% and live, on average, for 4.2 years.”
§ Microglial signatures and their role in health and disease > Abstract
What the sources say
- Not checked yetcites [15] Reu, P. et al. The lifespan and turnover of microglia in the human brain. Cell Rep. 20, 779–784 (2017). source
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In the paper
“not all microglia express triggering receptor expressed on myeloid cells 2 (TREM2)57, an immune receptor that is found in brain microglia and, when mutated, is a risk factor for non-familial AD58.”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Microglial heterogeneity and plasticity
What the sources say
- Not checked yetcites [57] Schmid, C. D. et al. Heterogeneous expression of the triggering receptor expressed on myeloid cells-2 on adult murine microglia. J. Neurochem. 83, 1309–1320 (2002). source
- Not checked yetcites [58] Colonna, M. & Wang, Y. TREM2 variants: new keys to decipher Alzheimer disease pathogenesis. Nat. Rev. Neurosci. 17, 201–207 (2016). source
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In the paper
“The origin of microglia has now been clearly defined and shown to relate to the early colonization of the CNS by mesodermal progenitors6 that arise from the yolk sac7,8”
§ Microglial signatures and their role in health and disease > Abstract
What the sources say
- Not checked yetcites [6] Kaur, C., Hao, A. J., Wu, C. H. & Ling, E. A. Origin of microglia. Microsc. Res. Tech. 54, 2–9 (2001). source
- Not checked yetcites [7] Alliot, F., Godin, I. & Pessac, B. Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res. Dev. Brain Res. 117, 145–152 (1999). source
- Not checked yetcites [8] Ginhoux, F. et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330, 841–845 (2010).References 7 and 8 identify microglia as originating from yolk-sac-derived primitive macrophages. source
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In the paper
“These findings suggest that, in AD, the ability of microglia to prune excess synapses in development is inappropriately activated and participates in synapse loss.”
§ Microglial signatures and their role in health and disease > Microglial physiological functions > Synaptic plasticity and synaptogenesis
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In the paper
“the development of microglia is dependent on CSF1R, which transmits signals upon activation by its ligands CSF1 and IL-34 and serves as a survival factor68.”
- Also stated in: § Mechanisms of homeostatic microglia regulation · plain
“It has also been shown that the development of microglia relies on the secondary transcription factor IFN regulatory factor 8 (IRF8), which is essential for the development of the mature microglia precursors known as A2 cells10”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Mechanisms of homeostatic microglia regulation
What the sources say
- Not checked yetcites [68] Wang, Y. et al. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat. Immunol. 13, 753–760 (2012). source
- Not checked yetcites [10] Kierdorf, K. et al. Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat. Neurosci. 16, 273–280 (2013).This study shows that microglia derived from erythromyeloid precursors develop into CD45 + c-kit lo CX 3 CR1 – immature (A1) cells and mature into CD45 + c-kit – CX 3 CR1 + (A2) cells. Both PU.1 and IRF8 transcription factors are vital for the development of A2 microglia. source
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In the paper
“the transcription factor MEF2C acts in homeostatic microglia to suppress the inflammatory response and that its expression declines during ageing in an interferon (IFN)-1-dependent manner77.”
- Also stated in: § Mechanisms of homeostatic microglia regulation · plain
“This study showed that loss of microglial MEF2C was linked to downregulation of CX3CR1, a molecule that is crucial for restraining immune responses in microglia78,79.”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Mechanisms of homeostatic microglia regulation
What the sources say
- Not checked yetcites [77] Deczkowska, A. et al. Mef2C restrains microglial inflammatory response and is lost in brain ageing in an IFN-I-dependent manner. Nat. Commun. 8, 717 (2017). source
- Not checked yetcites [78] Cardona, A. E. et al. Control of microglial neurotoxicity by the fractalkine receptor. Nat. Neurosci. 9, 917–924 (2006). source
- Not checked yetcites [79] Limatola, C. & Ransohoff, R. M. Modulating neurotoxicity through CX3CL1/CX3CR1 signaling. Front. Cell. Neurosci. 8, 229 (2014). source
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In the paper
“CNS-conditional Tgfb1−/− mice exhibit motor deficits, a loss of homeostatic microglia and the appearance of peripherally derived monocytes in the CNS25.”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Mechanisms of homeostatic microglia regulation
What the sources say
- Not checked yetcites [25] Butovsky, O. et al. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat. Neurosci. 17, 131–143 (2014).This study identifies the molecular and functional signature of homeostatic microglia, which depends on TGFβ signalling. source
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In the paper
“BDNF secreted by microglia caused a shift in the neuronal anion gradient underlying neuropathic pain100.”
- Also stated in: § Trophic support · plain
“The secretion of BDNF by microglia is suppressed by IL-1β101.”
§ Microglial signatures and their role in health and disease > Microglial physiological functions > Trophic support
What the sources say
- Not checked yetcites [100] Coull, J. A. et al. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438, 1017–1021 (2005). source
- Not checked yetcites [101] Tong, L. et al. Brain-derived neurotrophic factor-dependent synaptic plasticity is suppressed by interleukin-1beta via p38 mitogen-activated protein kinase. J. Neurosci. 32, 17714–17724 (2012). source
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- Also stated in: § Trophic support · plain
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In the paper
“the cytokine CSF1, acting via its receptor CSF1R, is important for microglial development8.”
- Also stated in: § Mechanisms of homeostatic microglia regulation · boosted
“interleukin-34 (IL-34), which is an additional ligand for CSF1R, promotes the tissue-specific signalling pathway that is required for the differentiation of myeloid cells that populate the skin and microglia in the CNS68.”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Mechanisms of homeostatic microglia regulation
What the sources say
- Not checked yetcites [8] Ginhoux, F. et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330, 841–845 (2010).References 7 and 8 identify microglia as originating from yolk-sac-derived primitive macrophages. source
- Not checked yetcites [68] Wang, Y. et al. IL-34 is a tissue-restricted ligand of CSF1R required for the development of Langerhans cells and microglia. Nat. Immunol. 13, 753–760 (2012). source
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In the paper
“These include the SMAD proteins, which are TGFβ1-dependent and contribute to establishing transcription of specific microglial genes75.”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Mechanisms of homeostatic microglia regulation
What the sources say
- Not checked yetcites [75] Gosselin, D. et al. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell 159, 1327–1340 (2014). source
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In the paper
“The transcription factor PU.1 serves as a master regulator of myeloid cells70. PU.1 plays a crucial role in determining macrophage lineages and microglial genesis and is a major factor in selecting the set of enhancers expressed by microglia.”
- Also stated in: § Mechanisms of homeostatic microglia regulation · plain
“PU.1 binds to the CSF1R promoter to drive gene transcription73 and to most enhancers in both mouse and human microglia.”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Mechanisms of homeostatic microglia regulation
What the sources say
- Not checked yetcites [70] Friedman, A. D. Transcriptional control of granulocyte and monocyte development. Oncogene 26, 6816–6828 (2007). source
- Not checked yetcites [73] Satoh, J., Asahina, N., Kitano, S. & Kino, Y. A. Comprehensive profile of ChIP-Seq-based PU.1/Spi1 target genes in microglia. Gene Regul. Syst. Bio. 8, 127–139 (2014).
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In the paper
“tonic activity of potassium channel subfamily K member 13 (KCNK13; also known as THIK1) promotes microglial ramification and surveillance of the brain parenchyma69.”
- Also stated in: § Mechanisms of homeostatic microglia regulation · plain
“Given that THIK1 is also required for the release of IL-1β by microglia”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Mechanisms of homeostatic microglia regulation
What the sources say
- Not checked yetcites [69] Madry, C. et al. Microglial ramification, surveillance, and interleukin-1ß release are regulated by the two-pore domain K(+) channel THIK-1. Neuron 97, 299–312 (2018). source
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In the paper
“Microglia secrete neurotrophic factors, such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), fibroblast growth factor (FGF) and insulin-like growth factor 1 (IGF1), that control the activity of receptor tyrosine kinases and are associated with signalling through phosphoinositide 3-kinase (PI3K)94.”
- Also stated in: § Trophic support · plain
“it was shown that microglia promote learning-dependent synapse formation through the secretion of BDNF in mice96.”
§ Microglial signatures and their role in health and disease > Microglial physiological functions > Trophic support
What the sources say
- Not checked yetcites [94] Shi, S. H., Jan, L. Y. & Jan, Y. N. Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity. Cell 112, 63–75 (2003). source
- Not checked yetcites [96] Parkhurst, C. N. et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155, 1596–1609 (2013). source
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In the paper
“Inhibition of complement reduces the number of phagocytic microglia as well as the extent of early synapse loss. Furthermore, the complement component C1q is needed for the toxic effects of Aβ oligomers92.”
§ Microglial signatures and their role in health and disease > Microglial physiological functions > Synaptic plasticity and synaptogenesis
What the sources say
- Not checked yetcites [92] Hong, S. et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352, 712–716 (2016). source
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In the paper
“Mice deficient in negative regulator of reactive oxygen species (NRROS), which is preferentially expressed in myeloid cells (including macrophages, neutrophils, microglia and perivascular macrophages) and regulates the production of reactive oxygen species, lack microglia and instead are populated by perivascular macrophage-like cells87.”
- Also stated in: § Mechanisms of homeostatic microglia regulation · plain
“The lack of microglia in mice lacking NRROS shows that this factor is important for the programme that generates the homeostatic microglial phenotype.”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Mechanisms of homeostatic microglia regulation
What the sources say
- Not checked yetcites [87] Wong, K. et al. Mice deficient in NRROS show abnormal microglial development and neurological disorders. Nat. Immunol. 18, 633–641 (2017). source
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In the paper
“In macrophages, MAFB promotes an anti-inflammatory phenotype, and its loss exacerbates inflammatory conditions80 and controls self-renewal81.”
- Also stated in: § Mechanisms of homeostatic microglia regulation · plain
“MAFB also antagonizes granulocyte-macrophage colony-stimulating factor (GM-CSF), which represses microglial differentiation83.”
- Also stated in: § Mechanisms of homeostatic microglia regulation · plain
“Furthermore, its expression is downregulated in the superoxide dismutase 1 (SOD1) mouse model of amyotrophic lateral sclerosis (ALS), in which inflammation is increased52,84.”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Mechanisms of homeostatic microglia regulation
What the sources say
- Not checked yetcites [80] Cuevas, V. D. et al. MAFB determines human macrophage anti-inflammatory polarization: relevance for the pathogenic mechanisms operating in multicentric carpotarsal osteolysis. J. Immunol. 198, 2070–2081 (2017). source
- Not checked yetcites [81] Soucie, E. L. et al. Lineage-specific enhancers activate self-renewal genes in macrophages and embryonic stem cells. Science 351, aad5510 (2016). source
- Not checked yetcites [83] Koshida, R., Oishi, H., Hamada, M. & Takahashi, S. MafB antagonizes phenotypic alteration induced by GM-CSF in microglia. Biochem. Biophys. Res. Commun. 463, 109–115 (2015). source
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In the paper
“the absence of TGFβ1, a factor known to be required for the in vitro development of the molecular signature characteristic of adult microglia, in the CNS results in a paralytic neurologic disease in mice25.”
- Also stated in: § Mechanisms of homeostatic microglia regulation · plain
“Importantly, TGFβ1 signalling has also been shown to be inhibited in microglia that are associated with neurodegeneration, in which the homeostatic signature is also suppressed52”
§ Microglial signatures and their role in health and disease > Homeostatic microglia > Mechanisms of homeostatic microglia regulation
What the sources say
- Not checked yetcites [25] Butovsky, O. et al. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat. Neurosci. 17, 131–143 (2014).This study identifies the molecular and functional signature of homeostatic microglia, which depends on TGFβ signalling. source
- Not checked yetcites [52] Krasemann, S. et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581 (2017).This study identifies a major microglial neurodegenerative phenotype in rodent and humans regulated by TREM2–ApoE signalling. source
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In the paper
“Microglia from transgenic mice that lack multifunctional protein 2 (MFP2) and thus model the peroxisomal β-oxidation deficiency common to ageing express inflammatory surface markers and downregulate the homeostatic purinergic receptor P2RY12 (REF.121) in the same manner as aged microglia27.”
- Also stated in: § Ageing · hedged
“In MFP2-deficient mice TGFβ receptor 1 (Tgfbr1) is downregulated, suggesting that the loss of homeostatic properties in ageing microglia is also related to the downregulation of this receptor121.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Ageing
What the sources say
- Not checked yetcites [121] Verheijden, S. et al. Identification of a chronic non-neurodegenerative microglia activation state in a mouse model of peroxisomal beta-oxidation deficiency. Glia 63, 1606–1620 (2015). source
- Not checked yetcites [27] Hickman, S. E. et al. The microglial sensome revealed by direct RNA sequencing. Nat. Neurosci. 16, 1896–1905 (2013). source
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In the paper
“Reactive gliosis and neural inflammation are hallmarks of AD4,122–125.”
- Also stated in: § Alzheimer disease · plain
“although not being the primary initiator of AD, microglia play an important cell-autonomous role in the disease.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Alzheimer disease
What the sources say
- Not checked yetcites [4] Sarlus, H. & Heneka, M. T. Microglia in Alzheimer’s disease. J. Clin. Invest. 127, 3240–3249 (2017). source
- Not checked yetcites [122] McGeer, P. L., Itagaki, S., Tago, H. & McGeer, E. G. Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci. Lett. 79, 195–200 (1987). source
- Not checked yetcites [123] Griffin, W. S. et al. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc. Natl Acad. Sci. USA 86, 7611–7615 (1989). source
- Not checked yetcites [124] Streit, W. J. Microglia and Alzheimer’s disease pathogenesis. J. Neurosci. Res. 77, 1–8 (2004). source
- Not checked yetcites [125] Streit, W. J., Mrak, R. E. & Griffin, W. S. Microglia and neuroinflammation: a pathological perspective. J. Neuroinflamm. 1, 14 (2004). source
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- Also stated in: § Alzheimer disease · plain
None of the sources cited for this claim have been checked yet.
In the paper
“Microglia contribute to neurogenesis in two ways: through phagocytosis of excessive newborn cells and by promoting neurogenesis through the secretion of cytokines.”
- Also stated in: § Neurogenesis · plain
“Phagocytosis is linked to the homeostatic microglial phenotype and is specifically dependent on the expression of receptor tyrosine kinase MerTK (MERTK), which is responsible for routine non-inflammatory clearance of dead brain cells in the neurogenic niche106.”
§ Microglial signatures and their role in health and disease > Microglial physiological functions > Neurogenesis
What the sources say
- Not checked yetcites [105] Sierra, A. et al. Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 7, 483–495 (2010). source
- Not checked yetcites [106] Fourgeaud, L. et al. TAM receptors regulate multiple features of microglial physiology. Nature 532, 240–244 (2016).This study shows that microglial MERTK is essential for elimination of apoptotic cells in neurogenic regions of the CNS. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one. The quote only partly states this claim.
- Also stated in: § Neurogenesis · plain
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
“Many of the microglial changes observed in ALS were also observed in an AD mouse model (see below), suggesting a common microglial response to different disease processes.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Amyotrophic lateral sclerosis
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It is known that microglia are also involved in oligodendrocyte development. A unique molecular signature of the microglia involved in regulating the development and homeostasis of oligodendrocytes and their progenitors has been identified and shown to be essential for these functions, as confirmed by microglial depletion experiments in mice110.”
- Also stated in: § Neurogenesis · boosted
“this ITGAX-expressing microglial subset has been shown to have a key role in myelinogenesis in the developing brain112.”
- Also stated in: § Neurogenesis · plain
“an ITGAX-expressing microglial subset was identified as the source of IGF1 in the developing brain112.”
§ Microglial signatures and their role in health and disease > Microglial physiological functions > Neurogenesis
What the sources say
- Not checked yetcites [110] Hagemeyer, N. et al. Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood. Acta Neuropathol. 134, 441–458 (2017). source
- Not checked yetcites [112] Wlodarczyk, A. et al. A novel microglial subset plays a key role in myelinogenesis in developing brain. EMBO J. 36, 3292–3308 (2017). source
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Also stated in: § Neurogenesis · boosted
In the paper
“Microglia attract monocytes to the brain in a CC-chemokine ligand 2 (CCL2)-dependent fashion. These monocytes play an important role in neuroinflammation but do not contribute to the resident microglial pool102.”
§ Microglial signatures and their role in health and disease > Microglial physiological functions > Chemotaxis and immune cell recruitment
What the sources say
- Not checked yetcites [102] Ajami, B., Bennett, J. L., Krieger, C., McNagny, K. M. & Rossi, F. M. Infiltrating monocytes trigger EAE progression, but do not contribute to the resident microglia pool. Nat. Neurosci. 14, 1142–1149 (2011).Using a parabiosis paradigm, this study shows that recruited monocytes do not contribute to the resident microglial pool. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The recruitment of CCR2-expressing monocytes also plays an important role in mouse models of AD, in which genetic deletion of CCR2 in mice impairs monocyte accumulation and accelerates disease progression103.”
§ Microglial signatures and their role in health and disease > Microglial physiological functions > Chemotaxis and immune cell recruitment
What the sources say
- Not checked yetcites [103] El Khoury, J. et al. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat. Med. 13, 432–438 (2007). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Microglia activated by IL-4 or IFNγ induced oligodendrogenesis or neurogenesis, respectively, from adult stem cell progenitor cells both in vivo and in vitro113. High, but not low, levels of IFNγ induced a microglial phenotype that impeded oligodendrogenesis. IL-4 reduced this impediment and overcame the blockage of IGF1 production that was caused by IFNγ113.”
§ Microglial signatures and their role in health and disease > Microglial physiological functions > Neurogenesis
What the sources say
- Not checked yetcites [113] Butovsky, O. et al. Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol. Cell. Neurosciences 31, 149–160 (2006). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“during the course of many diseases, microglia lose their homeostatic molecular signature and functions26,84,114, such as their roles in synaptic plasticity115, and become chronically inflammatory116.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing
What the sources say
- Not checked yetcites [26] Holtman, I. R. et al. Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis. Acta Neuropathol. Commun. 3, 31 (2015). source
- Not checked yetcites [84] Butovsky, O. et al. Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1 mice. Ann. Neurol. 77, 75–99 (2015).This study validates miR-155 as a therapeutic target to modulate microglia in a mouse model and in human ALS. source
- Not checked yetcites [114] Moore, C. S. et al. P2Y12 expression and function in alternatively activated human microglia. Neurol. Neuroimmunol. Neuroinflamm. 2, e80 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Aged microglia display a dystrophic phenotype118–120. It is also known that ageing, similar to neurodegeneration, induces a hypersensitive, pro-inflammatory microglial phenotype that some have referred to as ‘primed microglia’26.”
- Also stated in: § Ageing · plain
“In ageing mice, most of the ‘sensome’ genes (which encode proteins involved in sensing endogenous ligands and microorganisms) that are expressed by homeostatic microglia are downregulated27.”
- Also stated in: § Ageing · hedged
“These cells also express pro-inflammatory cell surface markers such as galectin 3 (LGALS3), tyrosine-protein kinase receptor UFO (AXL), CLEC7A, major histocompatibility complex (MHC) class II molecules and CXC-chemokine receptor 4 (CXCR4)26 and appear immunologically activated but not polarized to a pro- or anti-inflammatory phenotype25.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Ageing
What the sources say
- Not checked yetcites [118] Streit, W. J., Sammons, N. W., Kuhns, A. J. & Sparks, D. L. Dystrophic microglia in the aging human brain. Glia 45, 208–212 (2004). source
- Not checked yetcites [119] Streit, W. J. Microglial senescence: does the brain’s immune system have an expiration date? Trends Neurosciences 29, 506–510 (2006).References 118 and 119 propose that microglial senescence is important for age-related decline in cognitive function. source
- Not checked yetcites [120] Flanary, B. E., Sammons, N. W., Nguyen, C., Walker, D. & Streit, W. J. Evidence that aging and amyloid promote microglial cell senescence. Rejuven. Res. 10, 61–74 (2007). source
- Not checked yetcites [26] Holtman, I. R. et al. Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis. Acta Neuropathol. Commun. 3, 31 (2015). source
- Not checked yetcites [27] Hickman, S. E. et al. The microglial sensome revealed by direct RNA sequencing. Nat. Neurosci. 16, 1896–1905 (2013). source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Ageing · plain
In the paper
“It has also been shown that infiltrating monocytes promote brain inflammation and exacerbate neuronal damage after status epilepticus104.”
§ Microglial signatures and their role in health and disease > Microglial physiological functions > Chemotaxis and immune cell recruitment
What the sources say
- Not checked yetcites [104] Varvel, N. H. et al. Infiltrating monocytes promote brain inflammation and exacerbate neuronal damage after status epilepticus. Proc. Natl Acad. Sci. USA 113, E5665–E5674 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“microglial expression of the complement receptor CR1 has been linked to late-onset AD137,138 and may reflect the microglial phagocytosis of synapses that has been proposed to contribute to AD pathogenesis.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Alzheimer disease
What the sources say
- Not checked yetcites [137] Thambisetty, M. et al. Effect of complement CR1 on brain amyloid burden during aging and its modification by APOE genotype. Biol. Psychiatry 73, 422–428 (2013). source
- Not checked yetcites [138] Lambert, J. C. et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat. Genet. 41, 1094–1099 (2009). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, in mice, peripheral monocytes can enter the brain, clear Aβ and affect disease pathology144, an effect that is lost in Ccr2−/− animals103.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Alzheimer disease
What the sources say
- Not checked yetcites [144] Simard, A. R., Soulet, D., Gowing, G., Julien, J. P. & Rivest, S. Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron 49, 489–502 (2006). source
- Not checked yetcites [103] El Khoury, J. et al. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat. Med. 13, 432–438 (2007). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“The neurotoxicity of microglial cells may also be related to their expression of tau, which is triggered by the deposition of Aβ in the brain and is known to be neurotoxic149.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Alzheimer disease
What the sources say
- Not checked yetcites [149] Heneka, M. T. et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 14, 388–405 (2015). source
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.
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
“It is important to note that there are likely to be multiple microglial phenotypes associated with disease and that DAM microglia as defined may have either beneficial or detrimental function.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Alzheimer disease
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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Probably not a substantial claim. The paper may give no 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
“Furthermore, with the deposition of Aβ, the phenotype of microglial cells becomes more neurotoxic118,146–148: they express several inflammatory cytokines, including IL-1β, IL-6, tumour necrosis factor (TNF) and CCL3 (also known as MIP1α)146.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Alzheimer disease
What the sources say
- Not checked yetcites [118] Streit, W. J., Sammons, N. W., Kuhns, A. J. & Sparks, D. L. Dystrophic microglia in the aging human brain. Glia 45, 208–212 (2004). source
- Not checked yetcites [146] Sastre, M., Klockgether, T. & Heneka, M. T. Contribution of inflammatory processes to Alzheimer’s disease: molecular mechanisms. Int. J. Dev. Neurosci. 24, 167–176 (2006). source
- Not checked yetcites [147] Perry, V. H., Cunningham, C. & Holmes, C. Systemic infections and inflammation affect chronic neurodegeneration. Nat. Rev. Immunol. 7, 161–167 (2007). source
- Not checked yetcites [148] Rojo, L. E., Fernandez, J. A., Maccioni, A. A., Jimenez, J. M. & Maccioni, R. B. Neuroinflammation: implications for the pathogenesis and molecular diagnosis of Alzheimer’s disease. Arch. Med. Res. 39, 1–16 (2008). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“In human MS, microglia lose the expression of the P2RY12 homeostatic microglial marker and adopt a pro-inflammatory phenotype that includes the expression of phagocytic-related markers (macrosialin (also known as CD68)), antigen presentation markers (MHC class I and II molecules and T lymphocyte activation antigen CD86) and proteins involved in the production of reactive oxygen species (cytochrome”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Multiple sclerosis
What the sources say
- Not checked yetcites [36] Zrzavy, T. et al. Loss of ‘homeostatic’ microglia and patterns of their activation in active multiple sclerosis. Brain 140, 1900–1913 (2017). source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Independent of the specific disease, it appears that, over time, microglia may transform into an activated state and that this change is related to signals from the periphery that occur with ageing or disease143.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Alzheimer disease
What the sources say
- Not checked yetcites [143] Hoeijmakers, L., Heinen, Y., van Dam, A. M., Lucassen, P. J. & Korosi, A. Microglial priming and Alzheimer’s disease: a possible role for (early) immune challenges and epigenetics? Front. Hum. Neurosci. 10, 398 (2016). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“These DAM microglia were shown to be generated through a two-step activation process in which homeostatic microglia first transition to an intermediate stage (known as stage 1 DAM) in a TREM2-independent manner, followed by a second TREM2-dependent transition to stage 2 DAM111.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Alzheimer disease
What the sources say
- Not checked yetcites [111] Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290 (2017).This study utilizes unbiased single-cell RNA-sequencing analysis to define DAM microglia. source
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.
In the paper
“DAM microglia have been observed in other conditions including ageing, ALS and frontotemporal dementia (FTD) and in an inducible CK-p25 mouse model of severe neurodegeneration”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Alzheimer disease
What the sources say
- Not checked yetcites [111] Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290 (2017).This study utilizes unbiased single-cell RNA-sequencing analysis to define DAM microglia. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Microglia are the only cells in the brain to express CX3CR1, which serves an immunomodulatory role in the homeostatic state and the genetic ablation of which results in neurotoxicity78.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Multiple sclerosis
What the sources say
- Not checked yetcites [78] Cardona, A. E. et al. Control of microglial neurotoxicity by the fractalkine receptor. Nat. Neurosci. 9, 917–924 (2006). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- 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
“These studies emphasize that cellular reprogramming of microglia occurs in response to neurodegeneration and that this process is related to unique underlying transcriptional programmes.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Alzheimer disease
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Consistent with this, it was found that TREM2 also affects microglial metabolic fitness: patients with AD carrying TREM2 risk variants and TREM2-deficient mice have abundant autophagic vesicles in their microglia178.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Not checked yetcites [178] Ulland, T. K. et al. TREM2 maintains microglial metabolic fitness in Alzheimer’s disease. Cell 170, 649–663 (2017). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Consistent with this, TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury in mice168.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Not checked yetcites [168] Mazaheri, F. et al. TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury. EMBO Rep. 18, 1186–1198 (2017). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Consistent with this, mice lacking CX3CR1 exhibit a transient reduction in the numbers of microglia present in the brain during the early postnatal period and a subsequent deficit in synaptic pruning associated with impaired social behaviour164.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Autism spectrum disorder
What the sources say
- Not checked yetcites [164] Zhan, Y. et al. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat. Neurosci. 17, 400–406 (2014). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Although molecular profiling of microglia in animal models of PD has yet to be attempted, activated microglia are known to be prominent in mouse models and in human PD160.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Parkinson disease
What the sources say
- Not checked yetcites [160] Joers, V., Tansey, M. G., Mulas, G. & Carta, A. R. Microglial phenotypes in Parkinson’s disease and animal models of the disease. Prog. Neurobiol. 155, 57–75 (2017). source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“it has been reported that α-synuclein-dependent activation of microglia may be linked to changes in the microbiome in both animal models and patients162.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Parkinson disease
What the sources say
- Not checked yetcites [162] Sampson, T. R. et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 167, 1469–1480 (2016). source
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.
In the paper
“It has been reported that TREM2 promotes microglial survival by activating the WNT-β-catenin signalling pathway167.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Not checked yetcites [167] Zheng, H. et al. TREM2 Promotes Microglial Survival by Activating Wnt/beta-Catenin Pathway. J. Neurosci. 37, 1772–1784 (2017). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“However, others have reported that Trem2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in AD mouse models173, which is seemingly inconsistent with the link between TREM2 loss-of-function mutations and an increased risk of AD.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Not checked yetcites [173] Jay, T. R. et al. TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models. J. Exp. Med. 212, 287–295 (2015). source
hedgeddirect- Asserted: fails — The authors may not put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“It binds to apoptotic neurons and increases TREM2-mediated microglial phagocytosis of neurons179.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Not checked yetcites [179] Atagi, Y. et al. Apolipoprotein E is a ligand for triggering receptor expressed on myeloid cells 2 (TREM2). J. Biol. Chem. 290, 26043–26050 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Indeed, in EAE it has been shown that TREM2 is upregulated in spinal cord microglia and that an anti-TREM2 antibody exacerbates disease172.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Not checked yetcites [172] Piccio, L. et al. Blockade of TREM-2 exacerbates experimental autoimmune encephalomyelitis. Eur. J. Immunol. 37, 1290–1301 (2007). source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Minocycline has been shown to specifically affect microglia153–155, and a trial in MS showed positive trends156, although minocycline worsened patients with ALS157.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Multiple sclerosis
What the sources say
- Not checked yetcites [153] Kobayashi, K. et al. Minocycline selectively inhibits M1 polarization of microglia. Cell Death Dis. 4, e525 (2013). source
- Not checked yetcites [154] Sriram, K., Miller, D. B. & O’Callaghan, J. P. Minocycline attenuates microglial activation but fails to mitigate striatal dopaminergic neurotoxicity: role of tumor necrosis factor-alpha. J. Neurochem. 96, 706–718 (2006). source
- Not checked yetcites [155] Ledeboer, A. et al. Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain 115, 71–83 (2005). source
- Not checked yetcites [156] Metz, L. M. & Eliasziw, M. Trial of minocycline in clinically isolated syndrome of multiple sclerosis. N. Engl. J. Med. 377, 789 (2017). source
- Not checked yetcites [157] Gordon, P. H. et al. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial. Lancet Neurol. 6, 1045–1053 (2007). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Phagocytosis of apoptotic neurons that were injected into the brain of naive mice suppressed the microglial homeostatic signature and resulted in a transcriptional profile that mimicked the molecular signature of MGnD microglia.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Not checked yetcites [52] Krasemann, S. et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581 (2017).This study identifies a major microglial neurodegenerative phenotype in rodent and humans regulated by TREM2–ApoE signalling. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Aβ-induced microglial activation is impaired in humanized transgenic mice expressing human R47H TREM2 (REF.169), and the R47H mutation impairs TREM2 binding to anionic lipids166.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Not checked yetcites [169] Song, W. M. et al. Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism. J. Exp. Med. 215, 745–760 (2018). source
- Not checked yetcites [166] Wang, Y. et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model. Cell 160, 1061–1071 (2015).This study demonstrates that microglial TREM2 is a sensor for lipids associated with fibrillar Aβ and its loss affects microglia and augments Aβ accumulation. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“In the absence of TREM2, it has been reported that microglia do not fully surround Aβ plaques and that Aβ plaques are more diffuse and associated with greater neuritic damage174.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Not checked yetcites [174] Wang, Y. et al. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. J. Exp. Med. 213, 667–675 (2016). source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Trem2 deficiency ameliorated amyloid pathology at early stages but exacerbated it at late stages, suggesting that TREM2 plays distinct roles at different stages of disease175.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Not checked yetcites [175] Jay, T. R. et al. Disease progression-dependent effects of TREM2 deficiency in a mouse model of Alzheimer’s disease. J. Neurosci. 37, 637–647 (2017).References 173–175 show time-dependent differential effects of TREM2-dependent microglial function in AD mouse models. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Although it is not entirely clear how TREM2 regulates microglial signature phenotypes, TREM2 is known to recognize phosphatidylserine on the surface of apoptotic or damaged cells and to initiate ApoE signalling52.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Not checked yetcites [52] Krasemann, S. et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581 (2017).This study identifies a major microglial neurodegenerative phenotype in rodent and humans regulated by TREM2–ApoE signalling. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings are consistent with the interpretation that TREM2 protects from AD by enabling microglia to surround and alter Aβ plaque structure, thereby limiting neuritic damage.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
hedgeddirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“As discussed above, microglia are damage sensors of the CNS and act as phagocytes for the routine, non-inflammatory clearance of dead brain cells.”
§ Microglial signatures and their role in health and disease > Therapeutic targeting of microglia
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In the tau model of neurodegeneration, genetic deletion of either Apoe or Trem2 also arrested neurodegeneration, demonstrating that this pathway negatively regulates the homeostatic signature182,183.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Not checked yetcites [182] Shi, Y. et al. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature 549, 523–527 (2017). source
- Not checked yetcites [183] Leyns, C. E. G. et al. TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy. Proc. Natl Acad. Sci. USA 114, 11524–11529 (2017).References 182 and 183 connect TREM2 and ApoE signalling with exacerbation of neuroinflammation and tauopathy. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As described in this article, microglia have now been redefined as having either a homeostatic or a disease-associated phenotype on the basis of their molecular signature, and many of the pathways that regulate these signatures have been elucidated.”
§ Microglial signatures and their role in health and disease > Conclusions
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Microglial expression of Axl is upregulated and Mer is downregulated in microglia exhibiting the MGnD phenotype52.”
§ Microglial signatures and their role in health and disease > Therapeutic targeting of microglia
What the sources say
- Not checked yetcites [52] Krasemann, S. et al. The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases. Immunity 47, 566–581 (2017).This study identifies a major microglial neurodegenerative phenotype in rodent and humans regulated by TREM2–ApoE signalling. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Similarly, an oral tyrosine kinase inhibitor (GW2580) inhibited CSF1R in the APP/PS1 mouse model of AD, which reduced microglial proliferation and the microglial inflammatory profile190.”
§ Microglial signatures and their role in health and disease > Therapeutic targeting of microglia
What the sources say
- Not checked yetcites [190] Olmos-Alonso, A. et al. Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology. Brain 139, 891–907 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Other biomarkers to measure microglial function could be present in the cerebrospinal fluid.”
§ Microglial signatures and their role in health and disease > Therapeutic targeting of microglia
hedged- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In addition, PLX3397 treatment was reported to reduce accumulation of intraneuronal Aβ, neuritic plaque deposition and pre-fibrillar oligomers in the same mouse model of AD186.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Not checked yetcites [186] Sosna, J. et al. Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer’s disease. Mol. Neurodegener. 13, 11 (2018). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Pharmacological targeting of CSF1R in this study also improved cognition and prevented synaptic degeneration190.”
§ Microglial signatures and their role in health and disease > Therapeutic targeting of microglia
What the sources say
- Not checked yetcites [190] Olmos-Alonso, A. et al. Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology. Brain 139, 891–907 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Treatment with PLX5622, which also targets CSF1R, prevented the association of microglia with plaques and improved cognition in the 3xTg-AD mouse model of AD189.”
§ Microglial signatures and their role in health and disease > Therapeutic targeting of microglia
What the sources say
- Not checked yetcites [189] Dagher, N. N. et al. Colony-stimulating factor 1 receptor inhibition prevents microglial plaque association and improves cognition in 3xTg-AD mice. J. Neuroinflamm. 12, 139 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“As outlined above, it is now recognized that microglia are resident cells of the nervous system that are independent from myeloid cells that migrate into the brain from the periphery.”
§ Microglial signatures and their role in health and disease > Therapeutic targeting of microglia
boosted- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Consistent with a potential detrimental role of microglia, it was shown that ablation of microglia by a compound (PLX3397) that inhibits CSF1R did not reduce plaque burden, although it did protect synapses185.”
§ Microglial signatures and their role in health and disease > Microglia in disease and ageing > Regulation of disease-associated microglial signatures
What the sources say
- Not checked yetcites [185] Spangenberg, E. E. et al. Eliminating microglia in Alzheimer’s mice prevents neuronal loss without modulating amyloid-beta pathology. Brain 139, 1265–1281 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“However, although some anti-inflammatory drugs have been shown to diminish neuroinflammation, few have direct functional effects on microglial activity192.”
§ Microglial signatures and their role in health and disease > Therapeutic targeting of microglia
What the sources say
- Not checked yetcites [192] Lleo, A., Galea, E. & Sastre, M. Molecular targets of non-steroidal anti-inflammatory drugs in neurodegenerative diseases. Cell. Mol. Life Sci. 64, 1403–1418 (2007). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On the basis of our current understanding of microglial physiology, these treatments would be expected to mediate their effects by modulating the microglial homeostatic signature.”
§ Microglial signatures and their role in health and disease > Therapeutic targeting of microglia
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Animals raised in a germ-free environment or mice treated with broad-spectrum antibiotics develop dysfunctional microglia, an effect that can be ameliorated with short-chain fatty acids.”
§ Microglial signatures and their role in health and disease > Therapeutic targeting of microglia
What the sources say
- Not checked yetcites [199] Erny, D. et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat. Neurosci. 18, 965–977 (2015). source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, TAM receptors may control microglial physiology and are potential targets for therapeutic intervention.”
§ Microglial signatures and their role in health and disease > Therapeutic targeting of microglia
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nonetheless, the distinction between homeostatic and disease-associated signatures is not absolute, particularly in terms of their impact on disease: some microglial disease signatures that are not homeostatic may in fact have beneficial roles in halting the disease process, as illustrated by the paradoxical findings with TREM2.”
§ Microglial signatures and their role in health and disease > Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“This study shows that microglial MERTK is essential for elimination of apoptotic cells in neurogenic regions of the CNS.”
§ Microglial signatures and their role in health and disease > References
What the sources say
- Not checked yetcites [106] Fourgeaud, L. et al. TAM receptors regulate multiple features of microglial physiology. Nature 532, 240–244 (2016).This study shows that microglial MERTK is essential for elimination of apoptotic cells in neurogenic regions of the CNS. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This study shows that transplanted macrophages from multiple tissues can express microglial genes in the brain; however, only those of yolk sac origin fully attain microglial identity.”
§ Microglial signatures and their role in health and disease > References
What the sources say
- Not checked yetcites [220] Bennett, F. C. et al. A combination of ontogeny and CNS environment establishes microglial identity. Neuron 98, 1170–1183 (2018).This study shows that transplanted macrophages from multiple tissues can express microglial genes in the brain; however, only those of yolk sac origin fully attain microglial identity. source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This report shows rapid repopulation of microglia following pharmacological depletion.”
§ Microglial signatures and their role in health and disease > References
What the sources say
- Not checked yetcites [188] Elmore, M. R. et al. Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain. Neuron 82, 380–397 (2014).This report shows rapid repopulation of microglia following pharmacological depletion. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“References 182 and 183 connect TREM2 and ApoE signalling with exacerbation of neuroinflammation and tauopathy.”
§ Microglial signatures and their role in health and disease > References
What the sources say
- Not checked yetcites [182] Shi, Y. et al. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature 549, 523–527 (2017). source
- Not checked yetcites [183] Leyns, C. E. G. et al. TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy. Proc. Natl Acad. Sci. USA 114, 11524–11529 (2017).References 182 and 183 connect TREM2 and ApoE signalling with exacerbation of neuroinflammation and tauopathy. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“This study demonstrates that PU.1 gene disruption affects a number of developmentally regulated haematopoietic processes and myeloid development.”
§ Microglial signatures and their role in health and disease > References
What the sources say
- Not checked yetcites [71] Anderson, K. L. et al. Myeloid development is selectively disrupted in PU.1 null mice. Blood 91, 3702–3710 (1998).This study demonstrates that PU.1 gene disruption affects a number of developmentally regulated haematopoietic processes and myeloid development. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“This study shows that classically activated neuroinflammatory microglia induce toxic astrocytes, which contribute to the death of neurons and oligodendrocytes in neurodegenerative disorders.”
§ Microglial signatures and their role in health and disease > References
What the sources say
- Not checked yetcites [150] Liddelow, S. A. et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481–487 (2017).This study shows that classically activated neuroinflammatory microglia induce toxic astrocytes, which contribute to the death of neurons and oligodendrocytes in neurodegenerative disorders. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This study shows that classically activated neuroinflammatory microglia induce toxic astrocytes, which contribute to the death of neurons and oligodendrocytes in neurodegenerative disorders.”
§ Microglial signatures and their role in health and disease > References
What the sources say
- Not checked yetcites [150] Liddelow, S. A. et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481–487 (2017).This study shows that classically activated neuroinflammatory microglia induce toxic astrocytes, which contribute to the death of neurons and oligodendrocytes in neurodegenerative disorders. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“References 118 and 119 propose that microglial senescence is important for age-related decline in cognitive function.”
§ Microglial signatures and their role in health and disease > References
What the sources say
- Not checked yetcites [118] Streit, W. J., Sammons, N. W., Kuhns, A. J. & Sparks, D. L. Dystrophic microglia in the aging human brain. Glia 45, 208–212 (2004). source
- Not checked yetcites [119] Streit, W. J. Microglial senescence: does the brain’s immune system have an expiration date? Trends Neurosciences 29, 506–510 (2006).References 118 and 119 propose that microglial senescence is important for age-related decline in cognitive function. source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This study demonstrates that microglial TREM2 is a sensor for lipids associated with fibrillar Aβ and its loss affects microglia and augments Aβ accumulation.”
§ Microglial signatures and their role in health and disease > References
What the sources say
- Not checked yetcites [166] Wang, Y. et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer’s disease model. Cell 160, 1061–1071 (2015).This study demonstrates that microglial TREM2 is a sensor for lipids associated with fibrillar Aβ and its loss affects microglia and augments Aβ accumulation. source
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 microglial signatures that have been identified to date will provide a basis to identify new therapeutic targets and to measure the effect of microglial-directed therapies.”
§ Microglial signatures and their role in health and disease > Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: unclear — It is unclear whether it could be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This study uses single-cell RNA-sequencing and bioinformatics to describe microglial transcriptome profiles and temporal stages of development in early, pre-adult microglia, which are regulated by distinct regulatory circuits.”
§ Microglial signatures and their role in health and disease > References
What the sources say
- Not checked yetcites [82] Matcovitch-Natan, O. et al. Microglia development follows a stepwise program to regulate brain homeostasis. Science 353, aad8670 (2016).This study uses single-cell RNA-sequencing and bioinformatics to describe microglial transcriptome profiles and temporal stages of development in early, pre-adult microglia, which are regulated by distinct regulatory circuits. source
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
“This study shows that transplanted macrophages from multiple tissues can express microglial genes in the brain; however, only those of yolk sac origin fully attain microglial identity.”
§ Microglial signatures and their role in health and disease > References
What the sources say
- Not checked yetcites [220] Bennett, F. C. et al. A combination of ontogeny and CNS environment establishes microglial identity. Neuron 98, 1170–1183 (2018).This study shows that transplanted macrophages from multiple tissues can express microglial genes in the brain; however, only those of yolk sac origin fully attain microglial identity. source
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
“This study describes the age-dependent and region-dependent transcriptional heterogeneity of microglia.”
§ Microglial signatures and their role in health and disease > References
What the sources say
- Not checked yetcites [59] Grabert, K. et al. Microglial brain region-dependent diversity and selective regional sensitivities to aging. Nat. Neurosci. 19, 504–516 (2016).This study describes the age-dependent and region-dependent transcriptional heterogeneity of microglia. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This study implicates innate immunity in AD through alteration of PU.1 core transcriptional regulation of microglia and blood monocytes.”
§ Microglial signatures and their role in health and disease > References
What the sources say
- Not checked yetcites [135] Huang, K. L. et al. A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer’s disease. Nat. Neurosci. 20, 1052–1061 (2017).This study implicates innate immunity in AD through alteration of PU.1 core transcriptional regulation of microglia and blood monocytes. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
The paper relies on this without support.
A common neurodegenerative microglial signature exists for diseases such as ALS, AD, and MS.
“At the present time, a common neurodegenerative microglial signature has been identified for diseases such as ALS, AD and MS.”
The paper relies on this without support.
Innate immune cells can protect against Alzheimer disease by reducing Aβ accumulation during early stages of disease.
“It is known that innate immune cells can protect against AD by reducing the accumulation of Aβ, which occurs during early stages of disease.”
Claims other papers make about this one
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In the citing paper
“Interestingly, when we tested expression of genes that show substantial changes in transgenic mice associated with AD (43,44) a number of aspects of gene expression were mimicked by anti-inflammatory IL-4 stimulation, particularly the increased expression of genes associated with the neurodegenerative signature, including Igf1, Itgax, Clec7a and Arg1 (58,59,61,84,86).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [59]
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
“Under normal conditions, they help maintain homeostasis by providing neurotrophic support and clearing harmful substances, such as amyloid plaques, through phagocytosis [8, 9, 10].”
From Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease (2026) · cites this paper as [8]
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
“Further gene expression comparisons to MODEL-AD and DAM datasets showed significant shifts in microglial phenotypes [8, 15].”
From Stabilizing the retromer complex rescues synaptic dysfunction and endosomal trafficking deficits in an Alzheimer’s disease mouse model (2025) · cites this paper as [8]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“ITGAX-positive microglia are a source of Igf1 expression (59).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [59]
The cited source says what the claim attributes to it.
In the citing paper
“By orchestrating gene expression, transcription factors influence whether microglia play protective or detrimental roles in maintaining brain homeostasis and responding to disease [8, 13].”
From Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease (2026) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“It is well established that microglial activation is facilitated by both intrinsic and extrinsic factors, leading to precise reprogramming of the microglial phenotype [58,59].”
From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [58]
The cited source says what the claim attributes to it.
In the citing paper
“Dysfunctional microglial activation has been implicated in AD, contributing to synaptic loss, neuronal damage, and chronic inflammation [1, 38, 39].”
From microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer’s disease patients (2026) · cites this paper as [38]
In the citing paper
“Microglia display diverse and dynamic phenotypic states and play a plethora of roles in development, adulthood (homeostasis), aging and diseases (Butovsky and Weiner, 2018; Prinz et al., 2019; Thion and Garel, 2020).”
From What is a cell type and how to define it? (2022) · cites this paper as Butovsky and Weiner, 2018
In the citing paper
“Igf1 is abundantly expressed by microglia during postnatal development, aging or following brain injuries and plays a vital role in promoting neuronal survival (59,63–66).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [59]
In the citing paper
“Our findings, in line with previous studies (59,68–71), show that Igf1 expression is inhibited by pro-inflammatory stimuli and enhanced in anti-inflammatory environments.”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [59]
In the citing paper
“Differences in gene expression profiles of different microglial populations have been recently described using single cell RNA-seq showing some microglial populations are selectively dependent on Trem2 (58–62).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [59]
In the citing paper
“Itgax/CD11C is an integrin or cell surface antigen, and is up-regulated in a number of recent RNA-seq studies in response to amyloid plaques (58,59,61,84).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [59]
In the citing paper
“Indeed, a series of recent studies identified transcriptional signatures in response to AD-associated pathology, neurodegeneration and apoptotic neurons, which were in part dependent on Trem2 and included Igf1, Csf1, Itgax, Clec7a and Arg1, at least in mice (58,59,61,84,86).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [59]
In the citing paper
“Intriguingly, P2ry13 and Gpr34, mouse orthologs of genes we identified in our human microglial gene set, are known to show down-regulation in so-called DAM (86–88) that are found in AD and other neurological disorders.”
From The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease (2019) · cites this paper as [86]
In the citing paper
“Microglia are a highly dynamic cell type that can undergo context-dependent functional adaptations [38].”
From microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer’s disease patients (2026) · cites this paper as [38]
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Metadata
- Authors
- Butovsky, O., & Weiner, H. L.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Butovsky, Oleg
- Weiner, Howard L.
- Venue
- Nature Reviews Neuroscience
- Published
- 2018-09-11
- Volume
- 19
- Issue
- 10
- Pages
- 622-635
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- PMC
- PMC7255106
- OpenAlex
- W2890187093
- Semantic Scholar
- 06b85485b0376c63afcb4391ad2551d9a4da8702
- Cited by
- 1,046
- References
- 225
- Citations by year
- 2026: 103 · 2025: 143 · 2024: 191 · 2023: 146 · 2022: 153 · 2021: 158 · 2020: 90 · 2019: 53 · 2018: 7
- FWCI
- 7.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG043975, R01AG040092, R01AG051812, R01AG054672)
- National Eye Institute (R01EY027921)
- National Institute of Neurological Disorders and Stroke (R21NS104609, R21NS101673, R01NS088137, R01NS136122)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- microglia, homeostatic microglia, disease-associated microglia, gene expression profiling, surface protein expression, microglial plasticity, neuroinflammation
- MeSH terms
- Animals, Central Nervous System, Homeostasis, Humans, Membrane Proteins, Microglia
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 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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