The DOI matches its Crossref record; 205 of the 205 references it cites were found in a registry or an index; 20 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
80 Not checked yet · 26 Own interpretation · 7 Supported · 6 No basis given · 4 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
The cited sources support only part of this claim — read each source’s verdict below.
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
- Partly supportedcites [158] sourceExperimental — accuracy not yet measured
The Results section, “Oligomeric α-synuclein interacts with TLR1/2” (page unavailable), says that higher-ordered oligomeric α-synuclein activates microglia through TLR1/2 heterodimers. The citing sentence omits that structural qualifier; the paper reports no appreciable TLR1 interaction for monomeric α-synuclein. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
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.
- 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
“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
- Supportedcites [130] source
The Abstract reports that, in 4-month-old TREM2-deficient 5XFAD mice, reduced microglial clustering accompanied more diffuse Aβ plaques and increased neuritic dystrophy. The Concluding remarks say TREM2-mediated microgliosis limits early plaque diffusion. The sentence assigns the later-accumulation clause to a separate pair of citations; this paper mentions a previously reported increase at 8 months but presents the proposed link to early barrier loss as a hypothesis. (LLM, conf=0.88)
- Supportedcites [131] source
The Results section on plaque compaction (page not provided) reports that weakening the microglial barrier in Trem2-deficient mice produced less compact plaques with longer fibrils projecting outward. The Results section on early filamentous plaques also describes microglial processes wrapping fibrils and capping their ends. This supports the early outward extension attributed to this source; the later Aβ accumulation clause has separate citations. (LLM, conf=0.88)
- Supportedcites [114] source
The citation is attached to the later Aβ-accumulation clause. The Results section (‘TREM2 modulates Aβ accumulation’; page unavailable) reports significantly greater hippocampal Aβ accumulation in TREM2-deficient 5XFAD mice at 8.5 months, while the Discussion links impaired plaque-associated microgliosis to reduced Aβ removal. This supports the cited clause in the mouse model; the paper is not needed to establish the separately cited early-spreading clause. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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.
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- 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.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“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]
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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.
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