The DOI matches its Crossref record; 205 of the 205 references it cites were found in a registry or an index; 16 of the 147 sources its claims cite were checked for support.
Microglia Function in the Central Nervous System During Health and Neurodegeneration
Open accessAbstract
Microglia are resident cells of the brain that regulate brain development, maintenance of neuronal networks, and injury repair. Microglia serve as brain macrophages but are distinct from other tissue macrophages owing to their unique homeostatic phenotype and tight regulation by the central nervous system (CNS) microenvironment. They are responsible for the elimination of microbes, dead cells, redundant synapses, protein aggregates, and other particulate and soluble antigens that may endanger the CNS. Furthermore, as the primary source of proinflammatory cytokines, microglia are pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. Alterations in microglia functionality are implicated in brain development and aging, as well as in neurodegeneration. Recent observations about microglia ontogeny combined with extensive gene expression profiling and novel tools to study microglia biology have allowed us to characterize the spectrum of microglial phenotypes during development, homeostasis, and disease. In this article, we review recent advances in our understanding of the biology of microglia, their contribution to homeostasis, and their involvement in neurodegeneration. Moreover, we highlight the complexity of targeting microglia for therapeutic intervention in neurodegenerative diseases.
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Claims the paper makes
82 Not checked yet · 26 Own interpretation · 6 Supported · 6 No basis given · 3 Partly supported · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, it curtails cytokine production in response to TLR ligands (122–124).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
- Partly supportedcites [122] sourceExperimental — accuracy not yet measured
The Results section on phagocytosis of apoptotic neurons (page unavailable) reports that TREM2 overexpression reduced TNF-α and IL-1β gene transcripts in microglia cocultured with apoptotic neurons. It does not show reduced cytokine production in response to TLR ligands. The Discussion (page unavailable) describes attenuation of TLR responses by ingestion of apoptotic cells, but does not establish that TREM2 causes that effect. (LLM, conf=0.86)
- Not checked yetcites [123] source
- Supportedcites [124] source
The section “TREM-2 inhibits TLR- and FcR-induced TNF production” reports that a TREM-2–DAP12 chimera inhibited TNF production after stimulation with CpG DNA or zymosan. It also reports that TREM-2 knockdown increased the number of TNF-producing macrophages after those stimuli. TNF is a cytokine, so these findings support the citing sentence. (LLM, conf=0.93)
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
Every source the paper cites for this claim was checked and supports it.
In the paper
“the identification of CR1 variants associated with an increased risk for AD”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
- Supportedcites [110] source
The GWAS discussion (passage [1], page not given) reports suggestive evidence associating a CR1 variant with Alzheimer’s disease and notes an independent genome-wide significant CR1 association. That supports the claim that CR1 variants are associated with AD risk, although this study’s own CR1 result was suggestive. (LLM, conf=0.87)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In mouse models of AD, complete TREM2 deficiency or TREM2 haploinsufficiency results in markedly less clustering of microglia around Aβ plaques (114, 128, 129).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
- Supportedcites [114] source
In the Results section, the paper reports fewer plaque-associated microglia in both Trem2+/− and Trem2−/− 5XFAD mice than in 5XFAD controls. It also reports markedly reduced microglial clusters around plaques with complete TREM2 deficiency in a second AD mouse model. (LLM, conf=0.93)
- Partly supportedcites [128] sourceExperimental — accuracy not yet measured
The Results section reports about 40% less microglial coverage around Aβ plaques in 3-month-old APPPS1-21 mice with one TREM2 allele than in mice with two. This supports the haploinsufficiency part of the sentence, but the paper does not test complete TREM2 deficiency. (LLM, conf=0.88)
- Partly supportedcites [129] sourceExperimental — accuracy not yet measured
In Results and Discussion, under “TREM2-deficient mice have reduced Aβ plaque–associated macrophages” (page unavailable), the paper reports a fivefold decrease in plaque-associated Iba1+ cells with complete deficiency and describes a smaller effect in haploinsufficient mice reported by Ulrich et al. (2014). But it identifies the reduced plaque-associated cells as macrophages and says parenchymal P2RY12+ microglia were not reduced, so the claim’s identification of them as microglia is not fully supported. (LLM, conf=0.87)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“several studies have indicated that mutated HTT has an important impact on microglia and neuroinflammation during HD pathogenesis (163).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia in Other Neurodegenerative Diseases
What the sources say
- Supportedcites [163] source
Section 3.2 states that mutant huntingtin is expressed in microglia and may directly cause inflammation. Section 3.1 reports microglial activation in presymptomatic carriers and an HD mouse model, supporting the citing sentence’s qualified summary of the studies. Page numbers are not provided in our copy. (LLM, conf=0.90)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
In the paper
“Microglia development and maintenance depend on constant engagement of colony stimulating factor 1 receptor (CSF1R), a receptor tyrosine kinase that transmits intracellular signals, such as activation of protein kinase B (also known as AKT) and extracellular signal-regulated kinases (ERK), that promote microglia proliferation and survival (5).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Development of CNS Mononuclear Phagocytes
What the sources say
- Not checked yetcites [5] 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Bone marrow–derived myeloid precursors do not contribute to the microglia pool.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Development of CNS Mononuclear Phagocytes
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.
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
“Microglia express many pattern-recognition receptors (PRRs) that detect pathogen-associated molecular patterns (PAMPs) or tissue damage–associated molecular patterns (DAMPs).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Microglia Express a Wide Range of Immune Receptors
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.
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
“They are responsible for the elimination of microbes, dead cells, redundant synapses, protein aggregates, and other particulate and soluble antigens that may endanger the CNS.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In fact, transcriptome studies show that microglia activation is varied and context dependent.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Functional States of Microglia: Beyond the M1/M2 Paradigm
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“During normal CNS function, microglia have a “resting,” or homeostatic, transcriptome profile that reflects a surveilling activity (36–41) (Figure 1).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Functional States of Microglia: Beyond the M1/M2 Paradigm
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Analysis of the microglia transcriptome in comparison with that of other tissue macrophages has revealed a strong influence of TGF-β signaling, which culminates in the activation of SMAD proteins that induce transcription of specific target genes, including the purinergic receptor P2Y12 (37, 38, 43).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Transcriptome and Regulomes Underpinning Programs Unique to Microglia
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Microglia also express several families of receptors that enable phagocytosis or endocytosis of apoptotic cells, protein aggregates, and lipoprotein particles. These receptors include scavenger receptors, such as CD36, SR1, and MARCO (20); LDL receptor family members, such as LDLR, ApoER2, and VLDL (21); and three receptor tyrosine kinases, Tyro3, Axl, and Mertk (TAM) (22).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Microglia Express a Wide Range of Immune Receptors
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Microglia express phagocytic and endocytic receptors that enable them to capture antigens. Microglia also have the lysosomal machinery required for processing antigens and express MHC class II and costimulatory molecules necessary for presentation of antigenic peptides. Thus, microglia can function as antigen-presenting cells (APCs).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA CONTRIBUTE TO THE FUNCTION OF A HEALTHY CNS > Do Microglia Function as Antigen-Presenting Cells?
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.
In the paper
“Thus, the microbiota is essential for microglia maturation and function.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > The Microbiota Affects Microglia
What the sources say
- Not checked yetcites [52] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The prion paradigm has been expanded to many neurodegenerative diseases, including Alzheimer disease (AD), Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and others (94).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > The Prion Paradigm
What the sources say
- Not checked yetcites [94] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Microglia enhance glutamate-induced LTD (75). When neurons release glutamate and activate microglial NMDA receptors, microglia turn on NADPH oxidase and release ROS, which induces serine/threonine protein phosphatase 2A (PP2A) in neurons. PP2A promotes the internalization of AMPA receptors, thereby weakening AMPA receptor–mediated synaptic transmission (Figure 2).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA CONTRIBUTE TO THE FUNCTION OF A HEALTHY CNS > Microglia-Derived Cytokines Regulate Synaptic Plasticity
What the sources say
- Not checked yetcites [75] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Recent transcriptional analysis of microglia from different regions of the healthy adult brain has revealed remarkable regional diversity of microglia beyond a core transcriptome (45).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Transcriptome and Regulomes Underpinning Programs Unique to Microglia
What the sources say
- Not checked yetcites [45] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Importantly, microglia shape neuronal synapses by phagocytosing dendritic spines that are not receiving inputs from synaptic contacts (66, 67).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA CONTRIBUTE TO THE FUNCTION OF A HEALTHY CNS > Microglia Control Synaptic Density and Connectivity
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Microglia are necessary for the proper assembly of complex neuronal networks.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA CONTRIBUTE TO THE FUNCTION OF A HEALTHY CNS > Microglia Are Involved in Neurogenesis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Studies in mice have shown that sex is associated with considerable differences in microglia during and after development (53, 54).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Microglia and Gender
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Microglia express multiple receptors that can bind Aβ and trigger inflammation, such as CD36 (105), TLR2, TLR4, TLR6 (17), and NLRP3 (106)”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia and Alzheimer Disease
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“an increased risk for developing AD is significantly associated with rare variants of innate immune receptors expressed in microglia, including TREM2 (107, 108), CD33 (109), and complement receptor 1 (CR1) (110)”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Microglia clearance of PrPSc requires the cooperation of astrocytes, which release MFGE8 that tags PrPSc-containing apoptotic cells for phagocytosis (93).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia in Prion Diseases
What the sources say
- Not checked yetcites [93] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“While microglial phagocytosis of Aβ may be beneficial”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia and Alzheimer Disease
What the sources say
- Not checked yetcites [17] 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Even more rare loss-of-function mutations of TREM2 or DAP12 cause a form of recessively inherited presenile dementia, called Nasu-Hakola disease (126, 127).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
- Not checked yetcites [126] source
- Not checked yetcites [127] 127. Paloneva J, Autti T, Hakola P, Haltia MJ. 2002. Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) . GeneReviews, updated Mar. 12, 2015, Univ. Wash., Seattle. https://www.ncbi.nlm.nih.gov/books/NBK1197/
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.
In the paper
“Lack of C1q, C3, or CR3 curbed microglia activation and synaptic loss during amyloid plaque deposition.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
- Not checked yetcites [139] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, CD33 and TREM2 have opposite effects.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, these results are consistent with the conclusion that inappropriate inhibition of microglia is deleterious in AD.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: In mice, CD33 deficiency reduces insoluble amyloid-beta 1-42 and amyloid plaques.
In the paper
“Conversely, another CD33 variant associated with protection from AD is expressed at relatively low levels, reducing CD33 inhibitory potential (138).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
- Not checked yetcites [138] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Recent studies have shown that TREM2 is cleaved from the microglial cell surface by proteases such as ADAM10 and ADAM17, generating a soluble form of TREM2 (133, 134).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
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.
In the paper
“In humans, CD33 transmits intracellular signals through cytoplasmic tyrosine-based motifs that recruit protein tyrosine phosphatases, such as SHP1 and SHP2 (27).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
- Not checked yetcites [27] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“has suggested that inappropriate synapsis phagocytosis by microglia may also contribute to AD progression.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“irradiation of the donor prior to transplantation may disturb the BBB, artificially facilitating brain engraftment of peripheral monocytes (146).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Alzheimer Disease and Macrophages
What the sources say
- Not checked yetcites [146] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“expression studies in human brain parenchyma found very modest correlations between CR1 expression and AD-associated CR1 genetic variants (142).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
- Not checked yetcites [142] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The transcriptional profile of microglia isolated from SOD1G93A transgenic mice revealed expression of both neuroprotective factors, such as progranulin and IGF-I, and neurotoxic factors, like NADPH oxidase (42).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Amyotrophic Lateral Sclerosis and Microglia
What the sources say
- Not checked yetcites [42] 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.
In the paper
“Lack of CCR2 reduced monocytes’ ability to reach the brain and remove Aβ deposits (144).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Alzheimer Disease and Macrophages
What the sources say
- Not checked yetcites [144] 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.
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
“Inhibition of the complement pathway may be beneficial not only in Aβ but also in Tau pathology.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“peripheral macrophages that infiltrate motor axons during disease progression may also be neurotoxic (152)”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Amyotrophic Lateral Sclerosis and Microglia
What the sources say
- Not checked yetcites [152] 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.
In the paper
“mice lacking Crry had lower levels of Tau phosphorylation in brain lysates (141).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
- Not checked yetcites [141] 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.
None of the sources cited for this claim have been checked yet.
In the paper
“In mouse models of AD and cerebral amyloid angiopathy, blood monocytes and perivascular macrophages were shown to contribute to Aβ clearance in brain parenchyma and vessels (143–145).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Alzheimer Disease and Macrophages
What the sources say
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.
None of the sources cited for this claim have been checked yet.
In the paper
“parabiosis studies using nonirradiated congenic marked mouse pairs have failed to detect significant infiltration of monocytes into the brain in AD models (130, 147).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Alzheimer Disease and Macrophages
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.
None of the sources cited for this claim have been checked yet.
In the paper
“accumulation of mutant SOD1 in microglia may further amplify their proinflammatory and neurotoxic activity (149, 150).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Amyotrophic Lateral Sclerosis and Microglia
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“α-Synuclein activates microglia through the TLR1/2 heterodimer (158).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia in Parkinson Disease
What the sources say
- Not checked yetcites [158] 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.
In the paper
“the detrimental effects of hyperactivated or dysfunctional microglia can be attenuated through CX3CR1 (162).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia in Parkinson Disease
What the sources say
- Not checked yetcites [162] 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.
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
“Most likely, the impact of microglia on ALS pathogenesis depends on whether they act at early or late stages of the disease.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Amyotrophic Lateral Sclerosis and Microglia
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Since TBK1 is highly expressed in myeloid cells, it is likely that TBK1 mutations affect the ability of microglia to degrade misfolded protein aggregates.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Amyotrophic Lateral Sclerosis and Microglia
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“It was shown that T cells that enter the spinal cord slow disease progression by directing microglia to express neurotrophic factors (154).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Amyotrophic Lateral Sclerosis and Microglia
What the sources say
- Not checked yetcites [154] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Analysis of peripheral blood monocyte transcriptomes from HD patients has revealed a proinflammatory phenotype, perhaps reflecting a priming effect of mutant HTT (165).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia in Other Neurodegenerative Diseases
What the sources say
- Not checked yetcites [165] Miller JR, 2016, Hum. Mol. Genet. 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.
In the paper
“A recent study has indicated that the detrimental role of microglia in α-synuclein pathology may be mediated by the phagocytic receptor Axl (23).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia in Parkinson Disease
What the sources say
- Not checked yetcites [23] 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.
In the paper
“genetic studies have identified the leucine-rich repeat kinase 2 (LRRK2) as one of the most commonly mutated genes in both idiopathic and familial PD (159).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia in Parkinson Disease
What the sources say
- Not checked yetcites [159] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“genetic studies have provided evidence that defects in autophagy predispose to ALS (156, 157).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Amyotrophic Lateral Sclerosis and Microglia
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“recent genetic analyses have identified the R47H variant of TREM2 as a risk factor for PD in addition to AD (161).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia in Parkinson Disease
What the sources say
- Not checked yetcites [161] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the AD-associated R47H variant of TREM2, which impairs microglial activation, survival, and proliferation, was also found to be a risk factor for sporadic ALS (155).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Amyotrophic Lateral Sclerosis and Microglia
What the sources say
- Not checked yetcites [155] 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.
In the paper
“Positron emission tomography (PET) studies in presymptomatic HD gene carriers showed increased microglial activation, which correlated with striatal neuronal dysfunction (164).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia in Other Neurodegenerative Diseases
What the sources say
- Not checked yetcites [164] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Regardless of whether microglia express MeCP, they contribute to Rett syndrome by causing excessive synaptic loss (180).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia and Psychiatric Diseases
What the sources say
- Not checked yetcites [180] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“this suggests that neuroinflammation may have a role in the pathogenesis of depression (97, 184).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia and Psychiatric Diseases
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“given the role of microglia in sculpting and regulating the strength of neuronal synapses, microglia dysfunction may contribute to the pathogenesis of these diseases.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia and Psychiatric Diseases
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“MeCP2 is also essential for the functions of astrocytes and microglia (176, 177).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia and Psychiatric Diseases
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.
None of the sources cited for this claim have been checked yet.
In the paper
“These diseases are associated not only with chronic and progressive neuronal loss, but also with dysfunction of innate immune cells that may contribute to pathogenesis (170–173).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Diseases of the Optic Nerve and Retina Associated with Neurodegeneration
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Microglia are likely to contribute to the therapeutic effects of these antibodies by phagocytosing opsonized plaques through Fc receptors.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“studies in mouse models suggest that CSF1R ligands, such as IL-34 and CSF1, may provide neuroprotective and survival signals in neurodegeneration by activating CSF1R on selected neuron populations rather than microglia (194).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
What the sources say
- Not checked yetcites [194] 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.
In the paper
“impairment of microglia activation, as observed in TREM2-deficient mice, reduces the efficacy of the anti-Aβ antibodies (190).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
What the sources say
- Not checked yetcites [190] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“it is increasingly clear that microglial activity during neurodegeneration does not fit the M1/M2 polarization paradigm.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Recent studies using animal models of depression have consistently reported microglial reactivity in different brain regions”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia and Psychiatric Diseases
What the sources say
- Not checked yetcites [185] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“CSF1R haploinsufficiency has been implicated in the pathogenesis of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (193).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
What the sources say
- Not checked yetcites [193] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the identification of many regulatory immune receptors on microglia, some of which are mutated in AD and other neurodegenerative diseases, provides a new opportunity to modulate microglia functions in diseases using specific antibodies or ligands.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 56
- Probably not a substantial claim. 2
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“TREM2 binds polyanions, particularly phospholipids and sulfatides that may be exposed in the brain during Aβ accumulation due to neuronal cell apoptosis and myelin damage (114).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
- Partly supportedcites [114] sourceExperimental — accuracy not yet measured
The Results and Discussion support TREM2 recognition of phospholipids, including phosphatidylserine exposed by damaged or apoptotic cells, and sulfatides released by damaged myelin. The Discussion suggests a possible interaction with polyanions. The supplied claim also names HDL, LDL, and ApoE, but our copy provides no support for TREM2 binding those; those additions do not appear in the printed citing sentence. (LLM, conf=0.86)
- Partly supportedcites [115] 115. Song W, Hooli B, Mullin K, Jin SC, Cella M, et al. 2016. Alzheimer's disease-associated TREM2 variants exhibit either decreased or increased ligand-dependent activation. Alzheimers Dement . In press. https://doi.org/10.1016/j.jalz.2016.07.004 sourceExperimental — accuracy not yet measured
Results §2.2 states that TREM2 binds polyanionic ligands such as phospholipids and reports activation by sulfatide. The cited paper does not establish the citing sentence’s further claim that these lipids may be exposed in the brain during Aβ accumulation because of neuronal apoptosis and myelin damage; pages are unavailable in our copy. (LLM, conf=0.84)
- Partly supportedcites [116] sourceExperimental — accuracy not yet measured
The Results report TREM2 binding to HDL and LDL particles and lipidated APOE. The cited sentence, however, attributes binding to polyanions—particularly phospholipids and sulfatides exposed during neuronal apoptosis or myelin damage—and the passages in our copy do not establish those specific ligands or that context (searched: polyanions, sulfatides, phospholipids, myelin damage). (LLM, conf=0.84)
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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“A rare arginine 47 histidine (R47H) variant of TREM2 is associated with an increased risk for AD (107, 108). This variant impairs binding of TREM2 to many phospholipid ligands (114, 125).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
- Supportedcites [107] source
The Results passage reports that the rare TREM2 variant encoding R47H was significantly associated with Alzheimer’s disease, with confirmation in additional analyses. The phospholipid-binding statement has separate citations (114, 125) and is not attributed to this source. (LLM, conf=0.94)
- Supportedcites [108] source
The cited paper supports the first sentence’s claim: the Results (Association of Variant with Alzheimer’s Disease) identify R47H as a rare TREM2 variant associated with significantly increased Alzheimer’s disease risk. The phospholipid-binding claim appears in a separate sentence with different citations (114, 125), so it is not attributed to this source. (LLM, conf=0.93)
- Supportedcites [114] source
The Introduction states that the rare R47H variant is associated with increased Alzheimer’s disease risk. The Results report reduced responses to several phospholipid ligands, and the Discussion states that R47H affected binding of multiple lipid ligands. Page numbers are not provided in our copy. (LLM, conf=0.92)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“in a mouse model of AD, complement was activated before plaque deposition and microglia were responsible for complement-mediated synaptic loss (139).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
- Supportedcites [139] source
The Abstract reports that C1q increased and associated with synapses before overt plaque deposition. It also reports that inhibiting C1q, C3, or the microglial complement receptor CR3 reduced early synapse loss, and that microglia engulfed synaptic material in a CR3-dependent process. These passages support the claim about pre-plaque complement activation and microglial mediation of complement-dependent synapse loss in AD mouse models. (LLM, conf=0.94)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“restraining microglial activation by ablating NF-κB signaling rescued motor neurons from microglia-mediated death in vitro and extended survival of SOD1G93A mice (151).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Amyotrophic Lateral Sclerosis and Microglia
What the sources say
- Supportedcites [151] source
The Results section on in vitro microglia–motor neuron co-cultures reports that inhibiting NF-κB in SOD1-G93A microglia fully rescued motor neuron survival. The in vivo Results report reduced inflammatory microglial markers and a 20-day increase in median survival in SOD1-G93A mice with reduced microglial NF-κB signaling. The in vivo intervention reduced signaling rather than completely eliminating it. (LLM, conf=0.91)
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.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“one study showed that microglial autophagy facilitates clearance of extracellular Aβ fibrils and reduces Aβ-induced NLRP3 activation (200).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
What the sources say
- Supportedcites [200] source
The Discussion states that microglial autophagy degrades extracellular Aβ fibrils and that impaired autophagy aggravates Aβ-induced NLRP3 inflammasome activation. This supports both parts of the citing sentence. No page number is provided in our copy. (LLM, conf=0.94)
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
None of the sources cited for this claim have been checked yet.
In the paper
“In the steady state, microglia are ramified cells with multiple branches and processes, which extend from the somata and terminate with bulbous endings. These processes are in continuous motion, protruding and retracting to cover long distances and survey large areas of the brain.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Resting and Activated Microglia Are Highly Dynamic
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“Larger injuries or inflammatory stimuli induce microglia to morph from a ramified to an amoeboid shape. Cell bodies enlarge while cell processes become shortened and cover more limited areas. Amoeboid morphology reflects a highly activated state associated with phagocytosis and proinflammatory function.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Resting and Activated Microglia Are Highly Dynamic
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.
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
“Alterations in microglia functionality are implicated in brain development and aging, as well as in neurodegeneration.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > Abstract
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: unclear — It is unclear why the paper says 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
“Fate-mapping studies have demonstrated that microglia originate from early myeloid progenitors in the embryonic yolk sac that migrate into the developing neural tube, where they proliferate, colonize the entire parenchyma, and subsist throughout the life span of the organism by slow division (1, 2).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Development of CNS Mononuclear Phagocytes
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
“Microglia serve as brain macrophages but are distinct from other tissue macrophages owing to their unique homeostatic phenotype and tight regulation by the central nervous system (CNS) microenvironment.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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
“Microglia are resident cells of the brain that regulate brain development, maintenance of neuronal networks, and injury repair.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Genetic defects in CSF1R and pharmacological blockade of CSF1R drastically reduce microglia numbers (5, 6).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Development of CNS Mononuclear Phagocytes
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.
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
“Furthermore, as the primary source of proinflammatory cytokines, microglia are pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, IL-34 and CSF1 are partially redundant, such that genetic defects in either IL-34 or CSF1 result in a partial reduction of microglial numbers.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Development of CNS Mononuclear Phagocytes
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In addition to immune receptors, microglia express multiple receptors for neurotransmitters and neuropeptides released by neurons that promote neural-glia communications (31). These receptors allow microglia to monitor neuronal activity by guiding microglia processes toward neuronal synapses in order to influence synaptic plasticity and sculpt dendritic spine density.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Microglia Express Receptors for Neurotransmitters
What the sources say
- Not checked yetcites [31] 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.
None of the sources cited for this claim have been checked yet.
In the paper
“In models of neurodegeneration, microglia express both neurotoxic and neuroprotective factors; genes involved in oxidative phosphorylation; and lysosome, ribosome, and spliceosome factors involved in responses to misfolded proteins, stress, and neuronal death or injury (36, 42) (Figure 1).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Functional States of Microglia: Beyond the M1/M2 Paradigm
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“M1 activation is a proinflammatory and neurotoxic state typically induced by simultaneous triggering of TLR and IFN-γ signaling pathways.”
- Also stated in: § Functional States of Microglia: Beyond the M1/M2 Paradigm · plain
“M2 activation describes the anti-inflammatory and healing activities of microglia.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Functional States of Microglia: Beyond the M1/M2 Paradigm
What the sources say
- Not checked yetcites [34] Appel SH, 2011, Acta Myol
- Not checked yetcites [35] 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: § Functional States of Microglia: Beyond the M1/M2 Paradigm · 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
“Although the M1 and M2 categories have been helpful for conceptualizing microglia activities in vitro, it is increasingly accepted that the M1/M2 paradigm is inadequate to describe microglia and macrophage activation in vivo, as microglia rarely display a significant bias toward either the M1 or M2 phenotype.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Functional States of Microglia: Beyond the M1/M2 Paradigm
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Recent studies of organotypic hippocampal slice cultures have shown that microglia are crucial for protection against NMDA-induced toxicity (84). ATP released by damaged neurons activates the microglia receptor P2X7, inducing secretion of TNF-α, which tempers NMDA-induced toxicity.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA CONTRIBUTE TO THE FUNCTION OF A HEALTHY CNS > Microglia Prevent Excitotoxicity
What the sources say
- Not checked yetcites [84] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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
“Though helpful, some of these markers may be modulated by activation and/or expressed in other cell types outside of the CNS; therefore, they may not be suitable for unequivocally identifying or targeting tissue-resident microglia.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Transcriptome and Regulomes Underpinning Programs Unique to Microglia
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.
None of the sources cited for this claim have been checked yet.
In the paper
“However, aging microglia display signs of dystrophy, including reduced ramification and short, tortuous, swollen processes (58). The ability of microglia to survey the brain and respond to insults also declines with aging (59).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > BIOLOGY OF MICROGLIA > Microglia and Aging
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Administration of DT and subsequent depletion of microglia in these mice caused a significant reduction in motor-learning-dependent glutamatergic excitatory synapses and impaired performance in multiple learning tasks. In this model, microglia-induced synaptic plasticity depended on BDNF secretion, which activated neuronal Trk, a key mediator of synaptic plasticity (Figure 2).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA CONTRIBUTE TO THE FUNCTION OF A HEALTHY CNS > Microglia-Derived Cytokines Regulate Synaptic Plasticity
What the sources say
- Not checked yetcites [77] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“AD is the most common form of senile dementia, characterized by lesions consisting of extracellular masses of amyloid β (Aβ) peptides and intracellular bundles of fibrillar Tau protein.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia and Alzheimer Disease
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Although ApoE is likely to influence AD through multiple mechanisms, an important effect is enhancement of phagocytosis of Aβ aggregates by microglia while tempering their inflammatory responses (102) (Figure 4).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia and Alzheimer Disease
What the sources say
- Not checked yetcites [102] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Lack of NLRP3, TLR, and IL-1β signaling in transgenic mouse models of AD that express human APP and presenilin 1 mutations, attenuates Aβ deposition and prevents cognitive defects (17).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia and Alzheimer Disease
What the sources say
- Not checked yetcites [17] source
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.
None of the sources cited for this claim have been checked yet.
In the paper
“TREM2 is transmembrane glycoprotein expressed in myeloid cells that transmits intracellular signals through two associated transmembrane adapters, DAP12 (also known as Tyrobp) and DAP10 (Hcst) (26, 111, 112).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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
“Neurodegenerative diseases hinge not only on misfolding of endogenous proteins, but also on protein clearance. Imbalance between generation and disposal of misfolded proteins leads to irreversible autopropagation.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > The Prion Paradigm
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: unclear — It is unclear why the paper says 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
“Prion diseases are associated with activation of microglia and astrocytes, which contribute to PrPSc clearance.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia in Prion Diseases
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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
“Microglia can alter the course of neurodegeneration by clearing misfolded proteins by phagocytosis or, conversely, by releasing inflammatory mediators that promote protein aggregation and neuron damage (Figure 3).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > The Prion Paradigm
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.
In the paper
“Subsequent studies in sporadic AD revealed that a polymorphism of apolipoprotein E (ApoE), the ApoE4 allele, is strongly associated with an increased risk of AD, whereas the ApoE2 allele is associated with protection (101).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia and Alzheimer Disease
What the sources say
- Not checked yetcites [101] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“chronic stimulation of microglia by Aβ may be deleterious and cause prolonged inflammation (Figure 3) (17)”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia and Alzheimer Disease
What the sources say
- Not checked yetcites [17] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“DAP12 recruits the protein tyrosine kinase Syk, which activates multiple downstream signaling mediators, including PLC-γ, PI-3K, and ERK (111, 112).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
- Not checked yetcites [111] source
- Not checked yetcites [112] Xing J, 2015, Res. Rep. Biochem.
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.
None of the sources cited for this claim have been checked yet.
In the paper
“TREM2 promotes proliferation (119), survival (119), and phagocytosis of apoptotic cells (120–122).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“a CD33 variant associated with an increased risk for AD is expressed at relatively high levels, increasing CD33 inhibitory effects on myeloid functions, such as internalization of the Aβ1–42 peptide (137).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
- Not checked yetcites [137] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that TREM2 signaling helps protect against AD but can cause harm in excess.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This weakening of microglial barriers around Aβ facilitates spreading and invasiveness of fibrillar amyloid at early stages of disease (130, 131) followed by later accumulation of Aβ during disease progression (114, 132).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
What the sources say
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.
None of the sources cited for this claim have been checked yet.
In the paper
“cerebrospinal fluid levels of soluble TREM2 are a potential biomarker for microglia activity in early-stage AD and correlate with neuronal injury markers (135, 136).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Regulatory Immune Receptors in Alzheimer Disease
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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, microglia in ALS have a distinct gene-expression signature that does not fit the M1/M2 paradigm but reflects microglial response to protein aggregates, stress, and neuronal cell death and partially overlaps with that of other neurodegenerative diseases”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Amyotrophic Lateral Sclerosis and Microglia
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“C9orf72 is required for the normal function of myeloid cells, and altered microglial function may contribute to neurodegeneration in carriers of C9orf72 expansion (153).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Amyotrophic Lateral Sclerosis and Microglia
What the sources say
- Not checked yetcites [153] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“LRRK2-deficient rats, in contrast, had no significant loss of neurons and reduced numbers of activated myeloid cells in the substantia nigra (160).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia in Parkinson Disease
What the sources say
- Not checked yetcites [160] 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.
It may state two separate claims as one.
In the paper
“In human, rare gain-of-function mutations of TBK1 are associated with normal tension glaucoma. These mutations may affect autophagy and phagocytic functions of microglia (157).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Diseases of the Optic Nerve and Retina Associated with Neurodegeneration
What the sources say
- Not checked yetcites [157] 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.
In the paper
“Mice lacking the homeobox gene Hoxb8 in all cells or only in myeloid and endothelial cells spend twice as much time grooming as do their littermates, leading to hair loss and skin lesions reminiscent of a human compulsive disorder known as trichotillomania (175).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia and Psychiatric Diseases
What the sources say
- Not checked yetcites [175] source
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.
In the paper
“Modulation of inflammation through the adenosine A2A receptor (A2AR) also prevented neuroinflammation and protected retinal ganglion cells in vitro and in vivo (174).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Diseases of the Optic Nerve and Retina Associated with Neurodegeneration
What the sources say
- Not checked yetcites [174] 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Studies have revealed microglial activation in depressed patients, with a greater magnitude of activation in individuals who completed suicide (181–183)”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Microglia and Psychiatric Diseases
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In a mouse model of glaucoma, the complement pathway is upregulated before retinal ganglion cell death, while induction of C1q deficiency protects from glaucoma (69).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA IN DEGENERATIVE DISEASES > Diseases of the Optic Nerve and Retina Associated with Neurodegeneration
What the sources say
- Not checked yetcites [69] 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.
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
“Moreover, M1 activation is not always detrimental nor is M2 activation necessarily beneficial.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Cholesterol-lowering statins (195) and other metabolic drugs (196) have been reported to subdue inflammatory microglial functions and have beneficial effects on cognitive function in mouse models of AD. Moreover, the results of observational and randomized trials in humans have shown conflicting results (195).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In models of AD, M1 functions promote removal of amyloid plaques, while M2 functions may facilitate amyloid spreading (187).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
What the sources say
- Not checked yetcites [187] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Oral administration of the RXR agonist bexarotene in a mouse model of AD facilitated rapid clearance of soluble Aβ (103). The therapeutic effect was linked to the induction of increased levels of ApoE. Moreover, a recent study showed that bexarotene induces TREM2 expression in microglia (197).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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, therapeutic agents that target microglia may have beneficial effects but also adverse effects.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“M1 microglia may be neurotoxic in some cases but promote axonal regeneration in others (186).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
What the sources say
- Not checked yetcites [186] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Humanized antibodies that target misfolded proteins, such as Aβ, have been developed and are currently being tested in clinical trials (188, 189).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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
“Microglial phagocytosis can also be a double-edged sword in neurodegeneration. On one hand, it may facilitate the clearance of misfolded proteins at disease onset; on the other hand, it may facilitate the spreading of pathogenic seeds during disease progression if protein digestion is impaired, or contribute to synapse loss if too many synapses are pruned.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Another recent study showed that microglial autophagy is involved in synaptic pruning and regulates behavior (201).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
What the sources say
- Not checked yetcites [201] 201. Kim HJ, Cho MH, Shim WH, Kim JK, Jeon EY, et al. 2016. Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects. Mol. Psychiatry. In press. https://doi.org/10.1038/mp.2016.103 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.
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
“given the role of complement in synaptic loss and the association of CR1 mutations in AD, targeting of complement components may be a valuable option for both Aβ and Tau pathologies.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
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
“Since AD is associated with hypomorphic mutations of TREM2 and hypermorphic mutations of CD33, antibodies activating TREM2 or blocking CD33 might be helpful in correcting microglial dysfunction.”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“two recent studies showed that brain-engrafted bone marrow–derived cells either do not acquire microglial functions or do so only after a long time (202, 203).”
§ Microglia Function in the Central Nervous System During Health and Neurodegeneration > MICROGLIA AS THERAPEUTIC TARGETS IN NEURODEGENERATION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Microglia can be stimulated by DAMPs such as ATP and DNA.
“Moreover, microglia can be stimulated by DAMPs, such as ATP and DNA.”
The paper relies on this without support.
In mice, CD33 deficiency reduces insoluble amyloid-beta 1-42 and amyloid plaques.
“Moreover, in mice, CD33 deficiency is associated with reduced levels of insoluble Aβ1–42 in the brain as well as fewer amyloid plaques.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Indeed, TREM2 is an important microglial molecule25,27,28 thought to be involved in the regulation of microglial signatures in disease1,58.”
From Microglial signatures and their role in health and disease (2018) · cites this paper as [1]
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
“CSF1R mutations also reduce microglia numbers in the human brain”
From Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program (2019) · cites this paper as Colonna and Butovsky, 2017
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
“Indeed, under pathological conditions, microglia can acquire a detrimental pro-inflammatory phenotype that actively contributes to neuroinflammation, express genes involved with phagocytosis and lipid metabolism [343], and phagocytose unwanted material and synapses [344].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [344]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“It has been reported that ApoE facilitates the microglial response to amyloid plaque pathology (31).”
From Therapeutic Idol reduction ameliorates amyloidosis and improves cognitive function in APP/PS1 mice (2020) · cites this paper as [31]
The cited source says what the claim attributes to it.
In the citing paper
“Numerous studies have highlighted the crucial contribution of microglia to brain homeostasis during aging and neurodegeneration (17, 18, 28, 30).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [28]
The cited source says what the claim attributes to it.
In the citing paper
“Microglia also contribute to the maintenance of brain homeostasis by clearing apoptotic cells in the brain via efferocytosis (27–29).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [28]
The cited source says what the claim attributes to it.
In the citing paper
“As in case of macrophages, microglia activation may be described as M1, initiated by TLR and IFN-γ signaling pathways, characterized by production of proinflammatory cytokines and chemokines, such as TNF-α, IL-6, IL-1β, IL-12, and CCL2, or M2, initiated by IL-4, IL-13, IL-10, and resulting in production of IL-10, TGF-β, and growth factors [225].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [225]
The cited source says what the claim attributes to it.
In the citing paper
“Microglia, resident myeloid cells in the central nervous system (CNS), play a pivotal role in maintenance of brain homeostasis, along with progression of neurodegenerative diseases (7).”
From Microglia express ABI3 in the brains of Alzheimer's disease and Nasu-Hakola disease (2017) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“Data also suggest that activated microglia may also secrete one or more factors leading to neurodegeneration (Leyns and Holtzman, 2017; Colonna and Butovsky, 2017).”
From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Colonna and Butovsky, 2017
In the citing paper
“TREM2 promotes phagocytosis of apoptotic neurons, proliferation, and survival of microglia, and has been implicated in dampening TLR-induced inflammatory responses (147-151).”
From Microglia in Alzheimer's disease (2017) · cites this paper as [147]
In the citing paper
“TREM2 has many ligands, including phospholipids and sulfatides, which are exposed on apoptotic or damaged cells, lipoprotein particles such as HDL and LDL, and APOE.”
From Microglia in Alzheimer's disease (2017) · cites this paper as [147]
In the citing paper
“AD risk variants in TREM2 impair the cell surface transport and expression of TREM2; some variants either impair or markedly enhance the binding of TREM2 to phospholipids, suggesting that balanced TREM2 function in AD is important to counteract disease progression (147).”
From Microglia in Alzheimer's disease (2017) · cites this paper as [147]
In the citing paper
“AD risk variants in TREM2 impair the cell surface transport and expression of TREM2; some variants either impair or markedly enhance the binding of TREM2 to phospholipids, suggesting that balanced TREM2 function in AD is important to counteract disease progression (147).”
From Microglia in Alzheimer's disease (2017) · cites this paper as [147]
In the citing paper
“AD risk variants in TREM2 impair the cell surface transport and expression of TREM2; some variants either impair or markedly enhance the binding of TREM2 to phospholipids, suggesting that balanced TREM2 function in AD is important to counteract disease progression (147).”
From Microglia in Alzheimer's disease (2017) · cites this paper as [147]
In the citing paper
“Microglia is the inherent immune effector cells in the central nervous system [30, 31].”
From Neuroprotective Effect of Ceftriaxone on MPTP‐Induced Parkinson’s Disease Mouse Model by Regulating Inflammation and Intestinal Microbiota (2021) · cites this paper as [30]
In the citing paper
“When brain tissue is damaged or stimulated by α-syn or bacteria and their metabolites in the brain, TLR4 is activated on microglia, and then, the NF-κB pathway is activated to promote the secretion of proinflammatory factors such as IL-6, IL-1β, and TNF-α; the ultimate outcome is the death of neurons [30, 32].”
From Neuroprotective Effect of Ceftriaxone on MPTP‐Induced Parkinson’s Disease Mouse Model by Regulating Inflammation and Intestinal Microbiota (2021) · cites this paper as [30]
In the citing paper
“Moreover, activated microglia can secrete toxic factors to directly or indirectly injure neurons (Colonna and Butovsky, 2017; Liddelow et al., 2017).”
From Microglia in Alzheimer’s disease (2018) · cites this paper as Colonna and Butovsky, 2017
In the citing paper
“However, this simplistic classification fails to capture the complexity of microglial responses in the context of neurodegenerative disease.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [9]
In the citing paper
“When α-syn accumulates outside of cells and is not properly cleared, it can activate microglia through PRRs, leading to the release of inflammatory cytokines.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [9]
Citations
Cites
1 retracted
Bialas, A. R., & Stevens, B. (2013) · Nature Neuroscience · doi:10.1038/nn.3560 · Cited by 519
RetractedFrom inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
Macrophage plasticity and polarization: in vivo veritas
Sica, A., & Mantovani, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59643 · Cited by 6,335
Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo
Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005) · Science · doi:10.1126/science.1110647 · Cited by 5,827
Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages
Ginhoux, F., Greter, M., Leboeuf, M., Nandi, S., See, P., Gokhan, S., Mehler, M. F., Conway, S. J., Ng, L. G., Stanley, E. R., et al. (2010) · Science · doi:10.1126/science.1194637 · Cited by 5,175
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089 · cited 1×
“Two proteins of the complement cascade, C1q and C3, tag unused synapses for microglia recognition via complement receptor 3 (CR3; a heterodimer of CD11b and CD18), or for direct lysis via the complement cascade (68, 69) (Figure 2).”
BackgroundATP mediates rapid microglial response to local brain injury in vivo
Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., Littman, D. R., Dustin, M. L., & Gan, W.-B. (2005) · Nature Neuroscience · doi:10.1038/nn1472 · Cited by 3,913
Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis
Yano, J. M., Yu, K., Donaldson, G. P., Shastri, G. G., Ann, P., Ma, L., Nagler, C. R., Ismagilov, R. F., Mazmanian, S. K., & Hsiao, E. Y. (2015) · Cell · doi:10.1016/j.cell.2015.02.047 · Cited by 3,614
Research works printed but not linked: 4
- Appel SH, 2011, Acta Myol, 30, 4
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- 127. Paloneva J, Autti T, Hakola P, Haltia MJ. 2002. Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) . GeneReviews, updated Mar. 12, 2015, Univ. Wash., Seattle. https://www.ncbi.nlm.nih.gov/books/NBK1197/
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Cited by
Sorted by citations
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204
Microglia in Alzheimer’s disease
Hansen, D. V., Hanson, J. E., & Sheng, M. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201709069 · Cited by 1,935
“PTK2B/Pyk2 Non–receptor tyrosine kinase; homologue of focal adhesion kinase Activated in microglia by fibrillar Aβ (Combs et al., 1999).”
BackgroundMicroglia in neurodegenerative diseases: mechanism and potential therapeutic targets
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01588-0 · Cited by 1,616
Microglia Biology: One Century of Evolving Concepts
Prinz, M., Jung, S., & Priller, J. (2019) · Cell · doi:10.1016/j.cell.2019.08.053 · Cited by 1,525
Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution
Masuda, T., Sankowski, R., Staszewski, O., Böttcher, C., Amann, L., Sagar, Scheiwe, C., Nessler, S., Kunz, P., van Loo, G., et al. (2019) · Nature · doi:10.1038/s41586-019-0924-x · Cited by 1,310
Metadata
- Authors
- Colonna, M., & Butovsky, O.
- Affiliations
- Washington University in St. Louis (US)
- Brigham and Women's Hospital (US)
- Venue
- Annual Review of Immunology
- Publisher
- Annual Reviews
- Published
- 2017-04-26
- Volume
- 35
- Issue
- 1
- Pages
- 441-468
- ISSN
- 0732-0582 (ISSN-L)
- 1545-3278
- PMC
- PMC8167938
- OpenAlex
- W2527645962
- Cited by
- 2,894
- References
- 205
- Citations by year
- 2026: 439 · 2025: 510 · 2024: 526 · 2023: 385 · 2022: 304 · 2021: 264 · 2020: 195 · 2019: 132 · 2018: 105 · 2017: 29
- FWCI
- 12.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- ALS Association (ALSA2087)
- Multiple Sclerosis Society (5092A1)
- National Institutes of Health
- National Institute on Aging (R01AG051812, RF1AG051485)
- National Institute of Neurological Disorders and Stroke (R01NS088137)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- microglia, neurodegeneration, neuroinflammation, microglial homeostasis, microglial phenotype, inflammatory cytokines, brain development, brain aging, microglia-targeted therapy, neurodegenerative diseases, synaptic pruning, phagocytosis
- MeSH terms
- Animals, Biological Therapy, Brain, Central Nervous System, Homeostasis, Humans, Cytokines, Microglia, Neurodegenerative Diseases, Neurogenic Inflammation
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 2026-10-05, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-05 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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