The DOI matches its Crossref record; 161 of the 162 references it cites were found in a registry or an index; none of the 112 sources its claims cite is checked for support yet.
Microglia in Alzheimer's disease
Open accessAbstract
Microglia are brain-resident myeloid cells that mediate key functions to support the CNS. Microglia express a wide range of receptors that act as molecular sensors, which recognize exogenous or endogenous CNS insults and initiate an immune response. In addition to their classical immune cell function, microglia act as guardians of the brain by promoting phagocytic clearance and providing trophic support to ensure tissue repair and maintain cerebral homeostasis. Conditions associated with loss of homeostasis or tissue changes induce several dynamic microglial processes, including changes of cellular morphology, surface phenotype, secretory mediators, and proliferative responses (referred to as an "activated state"). Activated microglia represent a common pathological feature of several neurodegenerative diseases, including Alzheimer's disease (AD). Cumulative evidence suggests that microglial inflammatory activity in AD is increased while microglial-mediated clearance mechanisms are compromised. Microglia are perpetually engaged in a mutual interaction with the surrounding environment in CNS; thus, diverse microglial reactions at different disease stages may open new avenues for therapeutic intervention and modification of inflammatory activities. In this Review, the role of microglia in the pathogenesis of AD and the modulation of microglia activity as a therapeutic modality will be discussed.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
89 Not checked yet · 7 Own interpretation · 1 No basis given
In the paper
“PRRs bind to different species of Aβ with various affinities (71).”
§ Microglia in Alzheimer's disease > Alzheimer's disease
What the sources say
- Not checked yetcites [71] 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
“Microglial-derived immune factors can induce a so-called A1 astrocyte phenotype that contributes to neuronal death through reduced trophic support, impaired clearance capacity, and release of toxins (69).”
§ Microglia in Alzheimer's disease > Microglia activation in AD
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Activated microglia along with immunoglobulins and complement components are closely associated with Aβ deposits in brains from AD patients and AD mouse models (58)(59)(60)(61)(62).”
§ Microglia in Alzheimer's disease > Microglia activation in AD
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.
In the paper
“microglia also were implicated in spreading tau aggregates through endocytosis (via phagocytosis) and exocytosis (via exosomes) in a nonsynaptic transmission pathway (68).”
§ Microglia in Alzheimer's disease > Microglia activation in AD
What the sources say
- Not checked yetcites [68] 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
“Stewart and colleagues demonstrated that Aβ-mediated release of proinflammatory factors and neurotoxicity partially involved signaling through the CD36/ TLR4/TRL6 complex (108).”
§ Microglia in Alzheimer's disease > Toll-like receptors
What the sources say
- Not checked yetcites [108] source
boostedconditional- 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
“TLRs bind both fibrillar and oligomeric forms of Aβ (74).”
§ Microglia in Alzheimer's disease > Toll-like receptors
What the sources say
- Not checked yetcites [74] Landreth, 2009, Toll-like receptors in Alzheimer’s disease, Curr Top Microbiol Immunol
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
“recent GWAS link several immune genes, particularly complement receptor-1 (CR1), CD33, and triggering receptor expressed on myeloid cells-2 (TREM2), with increased AD risk (55).”
§ Microglia in Alzheimer's disease > Loss of inhibitory signals
What the sources say
- Not checked yetcites [55] 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
“These findings raise the possibility that innate immune activation may actively contribute to AD pathogenesis, rather than arising as a pure bystander reaction to amyloid deposition, as previously assumed (57).”
§ Microglia in Alzheimer's disease > Loss of inhibitory signals
What the sources say
- Not checked yetcites [57] 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
“a network-based integrative analysis of AD-related genes revealed that an immune/microglial gene network had the strongest association with AD neuropathology (56).”
§ Microglia in Alzheimer's disease > Loss of inhibitory signals
What the sources say
- Not checked yetcites [56] 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
“APOE4 expression was associated with enhanced Aβ production, driven by increasing APP expression in neurons (54).”
§ Microglia in Alzheimer's disease > Loss of inhibitory signals
What the sources say
- Not checked yetcites [54] 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
“studies elucidating the role of TLRs in microglial activation have yielded conflicting results (109).”
§ Microglia in Alzheimer's disease > Toll-like receptors
What the sources say
- Not checked yetcites [109] 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
“epidemiological studies supported that NSAIDs decrease the development of AD (105).”
§ Microglia in Alzheimer's disease > Multifaceted immune activation
What the sources say
- Not checked yetcites [105] 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
“Taken together, the authors suggested a bimodal distribution of microglial activation in the trajectory of AD, with an early protective peak at the preclinical/prodromal stage and a later cidal proinflammatory phenotype peaking at the clinical stage (102).”
§ Microglia in Alzheimer's disease > Multifaceted immune activation
What the sources say
- Not checked yetcites [102] Fan, 2017, An early and late peak in microglial activation in Alzheimer’s disease trajectory, Brain
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
“A drawback of TLR4 stimulation was the observed increase in taurelated pathology in 3xTgAD and rTg4510 mice (109).”
§ Microglia in Alzheimer's disease > Toll-like receptors
What the sources say
- Not checked yetcites [109] 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
“in MCI, microglial activation was positively correlated with cognition and gray matter volume, suggesting that microglial activation plays a protective role in the early phase of clinically apparent disease (100).”
§ Microglia in Alzheimer's disease > Multifaceted immune activation
What the sources say
- Not checked yetcites [100] Hamelin, 2016, Early and protective microglial activation in Alzheimer’s disease: a prospective study using 18F-DPA-714 PET imaging, Brain 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.
None of the sources cited for this claim have been checked yet.
In the paper
“In a mouse model of AD, overexpression of soluble complement component 3b/4b receptor 1-like (CRRY; a complement inhibitor in rodents) (122), C3 deficiency (123), or blocking of C5a (124), a downstream component of the complement cascade, increased Aβ levels in the absence of increased Aβ production, reflecting the role of complement in microglial phagocytosis.”
§ Microglia in Alzheimer's disease > Complement system
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.
In the paper
“Hong and colleagues demonstrated that microglia in concert with complement caused early synapse loss when challenged with oligomeric Aβ (121).”
§ Microglia in Alzheimer's disease > Complement system
What the sources say
- Not checked yetcites [121] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The discrepancies among these studies underscore the impact of the precise disease time period on complement-mediated regulation of microglial”
§ Microglia in Alzheimer's disease > Complement system
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
“Blocking of C3, C1q, or CR3 rescued this early synapse loss in APP/PS1 mice (121).”
§ Microglia in Alzheimer's disease > Complement system
What the sources say
- Not checked yetcites [121] 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
“Before the onset of Aβ deposition, microglia engulf synapses opsonized with the complement factors C1q and C3 upon CR3-mediated recognition of C3 (121).”
§ Microglia in Alzheimer's disease > Complement system
What the sources say
- Not checked yetcites [121] 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
“In the same studies, complement blockade was associated with increased neurodegeneration.”
§ Microglia in Alzheimer's disease > Complement system
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.
None of the sources cited for this claim have been checked yet.
In the paper
“Given the role of microglia and complement in synaptic pruning and the identification of a CR1 gene variant that is linked to an increased risk for AD (17, 120), complement-mediated microglial phagocytosis of synapses may contribute to AD pathogenesis.”
§ Microglia in Alzheimer's disease > Complement system
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
“Thus, cytokines could serve as potential therapeutic targets to modulate microglial responses.”
§ Microglia in Alzheimer's disease > Cytokines
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
“the inhibition of proinflammatory response, including loss of NLRP3 inflammasome, myeloid-related protein-14 (MRP14), and IL-12 and IL-23 signaling, has also been beneficial in reducing amyloid pathology (130).”
§ Microglia in Alzheimer's disease > Cytokines
What the sources say
- Not checked yetcites [130] 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
“This striking difference between human and mouse supports the idea that rodent microglia may not experience pathological factors associated with aging such as senescence or dystrophy (70).”
§ Microglia in Alzheimer's disease > Complement system
What the sources say
- Not checked yetcites [70] Streit, 2014, Microglial pathology, Acta Neuropathol Commun 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
“mice overexpressing IL-6 (127) or IFN-γ (128) had enhanced microglial phagocytosis of Aβ accompanied by an increase in complement component mRNA levels, TNF-α, and other inflammatory mediators.”
§ Microglia in Alzheimer's disease > Cytokines
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
“CSF1R signaling in a selected neuron population, rather than in microglia, provides neuroprotective and survival signals in the neurodegeneration setting (146).”
§ Microglia in Alzheimer's disease > Complement system
What the sources say
- Not checked yetcites [146] 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
“Stimulation of nuclear receptor signaling with the retinoid X receptor agonist bexarotene induces the TREM2 expression in microglia (153).”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [153] 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
“Allelic variants of TREM2 confer high risk for developing sporadic AD; therefore, research into TREM2's function has gained momentum.”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [55] 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
“Microglia receive signals for survival and proliferation following stimulation of the CSF1 receptor (CSF1R) with CSF1 or IL-34 (142).”
§ Microglia in Alzheimer's disease > Complement system
What the sources say
- Not checked yetcites [142] 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
“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.”
§ Microglia in Alzheimer's disease > TREM2
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.
In the paper
“TREM2 levels were elevated in the microglia of AD patients, particularly in microglia associated with plaques and neurofibrillary changes, and TREM2 levels correlated with markers of neurodegeneration (154), suggesting a pathogenic role for TREM2.”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [154] 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
“TREM2 levels were elevated in the microglia of AD patients, particularly in microglia associated with plaques and neurofibrillary changes, and TREM2 levels correlated with markers of neurodegeneration (154), suggesting a pathogenic role for TREM2.”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [154] 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.
In the paper
“TREM2 levels were elevated in the microglia of AD patients, particularly in microglia associated with plaques and neurofibrillary changes, and TREM2 levels correlated with markers of neurodegeneration (154), suggesting a pathogenic role for TREM2.”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [154] 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
“TREM2 deficiency eliminated plaque-associated CD45 hi LyC + myeloid cells, leading to reduced inflammation and AD-like pathology in these mice (155); however, TREM2-expressing myeloid cells were enriched in microglia processes contacting amyloid deposits in AD mice, and TREM2 deletion resulted in less compact plaques and increased dystrophic neurites.”
§ Microglia in Alzheimer's disease > TREM2
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
“TREM2 deficiency eliminated plaque-associated CD45 hi LyC + myeloid cells, leading to reduced inflammation and AD-like pathology in these mice (155); however, TREM2-expressing myeloid cells were enriched in microglia processes contacting amyloid deposits in AD mice, and TREM2 deletion resulted in less compact plaques and increased dystrophic neurites.”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [155] 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
“TREM2 deficiency eliminated plaque-associated CD45 hi LyC + myeloid cells, leading to reduced inflammation and AD-like pathology in these mice (155); however, TREM2-expressing myeloid cells were enriched in microglia processes contacting amyloid deposits in AD mice, and TREM2 deletion resulted in less compact plaques and increased dystrophic neurites.”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [155] 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
“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).”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [147] 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
“Studies on TREM2 deficiency in AD mice have produced conflicting results, with reports that Aβ pathology could be either increased or decreased.”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the 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).”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [147] 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.
In the paper
“TREM2 deficiency eliminated plaque-associated CD45 hi LyC + myeloid cells, leading to reduced inflammation and AD-like pathology in these mice (155); however, TREM2-expressing myeloid cells were enriched in microglia processes contacting amyloid deposits in AD mice, and TREM2 deletion resulted in less compact plaques and increased dystrophic neurites.”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [155] 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
“Similarly, TREM2 silencing in P301S mice increased tau pathology and synapse loss and enhanced the proinflammatory cytokine levels in the brain (156).”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [156] 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
“Interestingly, entraining gamma oscillation at 40 Hz in 5xFAD mice induced amyloid reductions that were associated with an increase in microglial numbers and morphological changes such as soma enlargement and shortening of processes loaded with Aβ.”
§ Microglia in Alzheimer's disease > Optogenics in activation of microglia
What the sources say
- Not checked yetcites [158] 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
“While TREM2 deficiency in young APP/PS1-21 mice ameliorated amyloid pathology, it enhanced amyloid deposition at later disease stages (157).”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [157] 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
“Additionally, TREM2 deficiency in aged mice decreased plaque-associated myeloid cell accumulation by reducing proliferation (157).”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [157] 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
“Interestingly, entraining gamma oscillation at 40 Hz in 5xFAD mice induced amyloid reductions that were associated with an increase in microglial numbers and morphological changes such as soma enlargement and shortening of processes loaded with Aβ.”
§ Microglia in Alzheimer's disease > Optogenics in activation of microglia
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: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“While TREM2 deficiency in young APP/PS1-21 mice ameliorated amyloid pathology, it enhanced amyloid deposition at later disease stages (157).”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [157] 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
“A recent report indicated that the opposing results from previous work might reflect a disease progression-dependent influence of TREM2 deficiency on AD pathology.”
§ Microglia in Alzheimer's disease > TREM2
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: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Similarly, TREM2 silencing in P301S mice increased tau pathology and synapse loss and enhanced the proinflammatory cytokine levels in the brain (156).”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [156] 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
“Similarly, TREM2 silencing in P301S mice increased tau pathology and synapse loss and enhanced the proinflammatory cytokine levels in the brain (156).”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [156] 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
“RNA sequencing analysis showed an increase in phagocytic genes, such as Cd68, β 2 -microglobulin (B2m), Icam, and lysozyme 2 (Lyz2), and in the proliferation markers Csf1, Csf1r, and Csf2ra.”
§ Microglia in Alzheimer's disease > Optogenics in activation of microglia
What the sources say
- Not checked yetcites [158] 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
“Additionally, TREM2 deficiency in aged mice decreased plaque-associated myeloid cell accumulation by reducing proliferation (157).”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [157] 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
“Notably, levels of proinflammatory genes (Il1b, Il6, Cd11b) and antiinflammatory genes (Igf1) were not changed (158), suggesting that it is possible to use immunomodulation to polarize microglia toward a beneficial activation state that is characterized by increased phagocytic activity without the induction of sustained inflammatory responses.”
§ Microglia in Alzheimer's disease > Optogenics in activation of microglia
What the sources say
- Not checked yetcites [158] 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.
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 data are not fully consistent, they strongly suggest that microglia could be mobilized to promote Aβ clearance and reduce amyloid deposition through multiple mechanisms.”
§ Microglia in Alzheimer's disease > Concluding remarks
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
“RNA sequencing analysis showed an increase in phagocytic genes, such as Cd68, β 2 -microglobulin (B2m), Icam, and lysozyme 2 (Lyz2), and in the proliferation markers Csf1, Csf1r, and Csf2ra.”
§ Microglia in Alzheimer's disease > Optogenics in activation of microglia
What the sources say
- Not checked yetcites [158] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A 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
“Interestingly, microglia seem to be intimately involved in the propagation of tau pathology; however, it remains unclear whether microglia contribute to tau pathology by failing to phagocytize pathological tau or by releasing factors that exacerbate tau pathology.”
§ Microglia in Alzheimer's disease > Concluding remarks
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.
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
“A plethora of evidence supports the dual nature of neuroinflammation in the early versus the late phases of AD.”
§ Microglia in Alzheimer's disease > Concluding remarks
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Additionally, the M1 or M2 microglia phenotypes could have a detrimental or beneficial outcome depending on the disease context, and more detailed analysis is required.”
§ Microglia in Alzheimer's disease > Concluding remarks
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
“Notably, levels of proinflammatory genes (Il1b, Il6, Cd11b) and antiinflammatory genes (Igf1) were not changed (158), suggesting that it is possible to use immunomodulation to polarize microglia toward a beneficial activation state that is characterized by increased phagocytic activity without the induction of sustained inflammatory responses.”
§ Microglia in Alzheimer's disease > Optogenics in activation of microglia
What the sources say
- Not checked yetcites [158] 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. 35
- Probably not a substantial claim. 4
In the paper
“Increased expression of Tlr2, Tlr4, Tlr5, Tlr7, and Tlr9 mRNAs was found in Aβ plaques, and expression of Tlr2/5 was elevated in plaque-associated tissue in comparison with plaquefree tissue (107)”
§ Microglia in Alzheimer's disease > Toll-like receptors
What the sources say
- Not checked yetcites [107] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Depletion of microglia suppressed tau propagation (68), suggesting that microglia actively contribute to tau pathology during AD pathogenesis.”
§ Microglia in Alzheimer's disease > Microglia activation in AD
What the sources say
- Not checked yetcites [68] 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.
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
“In AD pathogenesis, microglia activation may play a dual role: on one side, acute microglial activation in some experimental paradigms leads to decreased Aβ accumulation by increasing phagocytosis or clearance.”
- Also stated in: § Alzheimer's disease · plain
“chronic activation of microglia contributes to neurotoxicity and synapse loss by triggering several proinflammatory cascades.”
§ Microglia in Alzheimer's disease > Microglia activation in AD
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.
- Also stated in: § Alzheimer's disease · plain
None of the sources cited for this claim have been checked yet.
In the paper
“activated microglia in AD show increased proliferation (63,64) and increased expression of inflammatory markers such as CD36, CD14, CD11c, MHC-II, and iNOS (65,66)”
§ Microglia in Alzheimer's disease > Microglia activation in AD
What the sources say
- Not checked yetcites [63] source
- Not checked yetcites [64] Olmos-Alonso, 2016, Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology, Brain source
- Not checked yetcites [65] Kamphuis, 2016, Transcriptional profiling of CD11c-positive microglia accumulating around amyloid plaques in a mouse model for Alzheimer’s disease, Biochim Biophys Acta source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In vivo imaging shows that microglia activation precedes the onset of AD (100) and is paralleled by increased levels of inflammatory markers in the cerebrospinal fluid (101)”
§ Microglia in Alzheimer's disease > Multifaceted immune activation
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
“the COX-1 inhibitor naproxen was beneficial in fast decliners only; in contrast, the selective COX-2 inhibitor celecoxib was beneficial in slow decliners but harmful in the fast-progressing group.”
§ Microglia in Alzheimer's disease > Multifaceted immune activation
What the sources say
- Not checked yetcites [105] 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
“repeated monthly injections of CpG-ODNs reduced amyloid deposition and cerebral amyloid angiopathy, and prevented cognitive deficits.”
§ Microglia in Alzheimer's disease > Toll-like receptors
What the sources say
- Not checked yetcites [116] 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
“These findings suggested that CD14 deletion shifts microglia activation to an immunomodulatory state, possibly by blocking TLR2 signaling, which contributes to inflammation and AD pathology (115).”
§ Microglia in Alzheimer's disease > Toll-like receptors
What the sources say
- Not checked yetcites [115] 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
“In contrast to TLR4 stimulation, TLR9 stimulation decreased tau-related pathology (116).”
§ Microglia in Alzheimer's disease > Toll-like receptors
What the sources say
- Not checked yetcites [116] 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
“COX-2 expression peaks in neurons in Braak phases 0-II (an early stage characterized by neurofibrillary changes beginning at transentorhinal regions), probably representing an adaptive response that subsequently declines (105).”
§ Microglia in Alzheimer's disease > Multifaceted immune activation
What the sources say
- Not checked yetcites [105] 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
“microglial activation correlated with glucose hypometabolism in AD patients (103), suggesting a link between microglial activation and synaptic dysfunction.”
§ Microglia in Alzheimer's disease > Multifaceted immune activation
What the sources say
- Not checked yetcites [103] Fan, 2015, Longitudinal influence of microglial activation and amyloid on neuronal function in Alzheimer’s disease, Brain 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.
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
“Hence, it seems that TLR9 stimulation activates an innate immune response that benefits AD pathology without provoking inflammation.”
§ Microglia in Alzheimer's disease > Microglia proliferation
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
“APP/PS1dE9 mice lacking functional TRL4 showed an increase in Aβ load associated with decreased expression of IL-1β, CCL3, and CCL4 and decreased cognitive function (110), suggesting a protective role of TRL4 in amyloid clearance.”
§ Microglia in Alzheimer's disease > Toll-like receptors
What the sources say
- Not checked yetcites [110] Song, 2011, TLR4 mutation reduces microglial activation, increases Aβ deposits and exacerbates cognitive deficits in a mouse model of Alzheimer’s disease, J Neuroinflammation 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.
None of the sources cited for this claim have been checked yet.
In the paper
“other studies have reported that inhibition of different components of complement impaired Aβ phagocytosis, resulting in elevated synapse loss.”
§ Microglia in Alzheimer's disease > Complement system
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.
In the paper
“Inhibition of microglial C3aR reduced microglial activation and augmented Aβ clearance in the brain (125), suggesting a detrimental role for complement.”
§ Microglia in Alzheimer's disease > Complement system
What the sources say
- Not checked yetcites [125] 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
“in the clinical phase of AD, the strong association between microglial activation and AD pathology was observed in young AD patients, but activation waned in AD patients older than 80 years (106)”
§ Microglia in Alzheimer's disease > Multifaceted immune activation
What the sources say
- Not checked yetcites [106] Hoozemans, 2011, Neuroinflammation in Alzheimer’s disease wanes with age, J Neuroinflammation source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Lian and colleagues demonstrated that Aβ induced release of C3 from astrocytes and impaired microglial Aβ phagocytosis (125).”
§ Microglia in Alzheimer's disease > Complement system
What the sources say
- Not checked yetcites [125] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“IL-1β, a key cytokine of the innate immune response, was shown to enhance Aβ pathology (126), as well as increase tau pathology (109).”
§ Microglia in Alzheimer's disease > Cytokines
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
“The NLRP3 inflammasome is critical for maturation of IL-1β, and loss of NLRP3 in APP/PS1 decreased amyloid burden (131).”
§ Microglia in Alzheimer's disease > Cytokines
What the sources say
- Not checked yetcites [131] Heneka, 2013, NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice, Nature 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.
In the paper
“Increased microglial proliferation was observed in several murine AD models (63), appearing with plaque onset and persisting for 18 months (63).”
§ Microglia in Alzheimer's disease > Microglia proliferation
What the sources say
- Not checked yetcites [63] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Lawson and colleagues reported a microglial turnover rate of 0.05% at any given time in healthy brain (141), but recent data from the same group indicated a turnover rate of 0.69% (7).”
§ Microglia in Alzheimer's disease > Complement system
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.
In the paper
“IL-10 levels are elevated in AD brain, and IL-10 overexpression in mice increased APOE expression in addition to worsening AD-related pathology and cognitive impairment (132).”
§ Microglia in Alzheimer's disease > Cytokines
What the sources say
- Not checked yetcites [132] 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
“microglia from TNFR-deficient 3xTgAD mice showed defective phagocytosis, highlighting the protective role of TNF-α in facilitating clearance mechanisms.”
§ Microglia in Alzheimer's disease > Cytokines
What the sources say
- Not checked yetcites [129] 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
“Il10 deletion led to increased Aβ phagocytosis and increased CD68 reactivity in Aβ depositassociated microglia (133).”
§ Microglia in Alzheimer's disease > Cytokines
What the sources say
- Not checked yetcites [133] 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
“Increased microglial proliferation has been described in the brains of AD patients (135), and in the prodromal stage of Parkinson disease (136), suggesting that microglial proliferation is an early event in the course of neurodegenerative diseases.”
§ Microglia in Alzheimer's disease > Microglia proliferation
What the sources say
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.
In the paper
“TNF receptor (TNFR) deficiency in 3xTgAD mice was associated with increased amyloid deposition and enhanced tau phosphorylation (129).”
§ Microglia in Alzheimer's disease > Cytokines
What the sources say
- Not checked yetcites [129] 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.
It may state two separate claims as one.
In the paper
“TREM2 deficiency impairs microglial phagocytosis of plaques opsonized with anti-Aβ antibodies, suggesting a critical role for TREM2 in the efficacy of antibody-based therapeutics (152).”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [152] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 phagocytosis of apoptotic neurons, proliferation, and survival of microglia, and has been implicated in dampening TLR-induced inflammatory responses (147-151).”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the CEBP/α/PU.1 pathway is involved in the regulation of monopoiesis and granulopoiesis (143, 144) and serves as a candidate for regulating proliferation in microglia.”
§ Microglia in Alzheimer's disease > Complement system
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Pharmacological inhibition of CSF1R in mice upregulated antiinflammatory mediators, including IL-4, IL-5, IL-13, and CCL9, and increased synapse and spine densities while reducing proinflammatory cytokine levels (64).”
§ Microglia in Alzheimer's disease > Complement system
What the sources say
- Not checked yetcites [64] Olmos-Alonso, 2016, Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology, Brain 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
“Although targeting CSF1R has therapeutic potential, caution should be taken, as CSF1R haploinsufficiency was linked to adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (145).”
§ Microglia in Alzheimer's disease > Complement system
What the sources say
- Not checked yetcites [145] 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.
It may state two separate claims as one.
In the paper
“TREM2 was upregulated in CD45 hi LyC + myeloid cells surrounding the amyloid plaques, but not in parenchymal P2Y12 + microglia (155).”
§ Microglia in Alzheimer's disease > TREM2
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.
It may state two separate claims as one.
In the 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).”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [147] 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
“TREM2 deficiency eliminated plaque-associated CD45 hi LyC + myeloid cells, leading to reduced inflammation and AD-like pathology in these mice (155); however, TREM2-expressing myeloid cells were enriched in microglia processes contacting amyloid deposits in AD mice, and TREM2 deletion resulted in less compact plaques and increased dystrophic neurites.”
§ Microglia in Alzheimer's disease > TREM2
What the sources say
- Not checked yetcites [155] 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
“Gamma oscillations arise from the activation of local circuits of excitatory and fast-spiking inhibitory neurons resonating at 20-50 Hz, and changes in gamma oscillation have been observed in neurological diseases (158).”
§ Microglia in Alzheimer's disease > Optogenics in activation of microglia
What the sources say
- Not checked yetcites [158] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Interestingly, entraining gamma oscillation at 40 Hz in 5xFAD mice induced amyloid reductions that were associated with an increase in microglial numbers and morphological changes such as soma enlargement and shortening of processes loaded with Aβ.”
§ Microglia in Alzheimer's disease > Optogenics in activation of microglia
What the sources say
- Not checked yetcites [158] 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.
It may state two separate claims as one.
In the paper
“Gamma oscillations arise from the activation of local circuits of excitatory and fast-spiking inhibitory neurons resonating at 20-50 Hz, and changes in gamma oscillation have been observed in neurological diseases (158).”
§ Microglia in Alzheimer's disease > Optogenics in activation of microglia
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: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“It seems that combining human induced pluripotent stem cell (iPSC) technology (159) with recent advances in gene editing will provide new opportunities to model disease pathology that more closely resembles human AD.”
§ Microglia in Alzheimer's disease > Concluding remarks
What the sources say
- Not checked yetcites [159] 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.
Probably not a substantial claim.
- The authors state this as an assumption: Existing mouse models do not show clear neurodegeneration or human-like tau pathology unless a tau mutation is used to induce the disease.
The authors state this as an assumption.
Aging strongly affects innate immunity and is a major risk factor for Alzheimer's disease.
“Given that age has a dramatic impact on innate immunity and represents a major risk factor for AD, more longitudinal studies need to be performed and the overall outcome of immune modulation needs to be tested in aged animals.”
The authors state this as an assumption.
Existing mouse models do not show clear neurodegeneration or human-like tau pathology unless a tau mutation is used to induce the disease.
“One limitation of current mouse models is the absence of clear neurodegeneration and human-like tau pathology unless the disease is induced by a tau mutation.”
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
“Neuroinflammation is a key contributor to AD progression. While early immune responses may aid in the clearance of Aβ and tau aggregates, prolonged activation of microglia and astrocytes leads to chronic inflammation and the release of pro-inflammatory cytokines such as IL-1β and TNF-α, promoting neuronal damage in vulnerable brain regions like the neocortex and hippocampus [34–36].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [34]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“For example, they facilitate the clearance of Aβ through phagocytosis42, yet they can also exacerbate neurodegeneration by driving persistent neuroinflammation43.”
From Deletion of SPI1 in microglia exacerbates amyloid pathology by impairing microglial response in Alzheimer’s disease models (2026) · cites this paper as [43]
The cited source says what the claim attributes to it.
In the citing paper
“Microglia are brain-resident innate immune effector cells and are widely thought to be the key mediators of amyloid beta clearance [14–16].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“Alzheimer's disease (AD) is characterized by the hallmark pathology comprised of widespread amyloid-β (Aβ) deposition, neurofibrillary tangle (NFT) formation, extensive neurodegeneration, and profound activation of microglia in the brain (6).”
From Microglia express ABI3 in the brains of Alzheimer's disease and Nasu-Hakola disease (2017) · cites this paper as [6]
In the citing paper
“In the early stages of AD, activated microglia cause phagocytosis and clearance of pathologic Aβ and/or tau, positively affecting AD pathologies in animal models [89, 90].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [89]
In the citing paper
“Microglia both exert protective function by phagocytosing and clearing pathological protein aggregates”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [2]
In the citing paper
“Microglia phagocytose misfolded proteins, cellular debris, and dying cells to maintain homeostasis.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [2]
In the citing paper
“Reactive gliosis and neural inflammation are hallmarks of AD4,122–125.”
From Microglial signatures and their role in health and disease (2018) · cites this paper as [4]
In the citing paper
“Microglia represent innate immune cells of the CNS that play important disease-modifying roles in neurodegeneration including Alzheimer’s disease (AD) [1–4].”
From Identification and therapeutic modulation of a pro-inflammatory subset of disease-associated-microglia in Alzheimer’s disease (2018) · cites this paper as [3]
In the citing paper
“Data from mouse models have suggested dual roles for microglia in AD: pro-inflammatory functions that promote neurotoxicity and amyloid β (Aβ) accumulation, opposed by amyloid-clearing and neuroprotective functions [3, 4].”
From Identification and therapeutic modulation of a pro-inflammatory subset of disease-associated-microglia in Alzheimer’s disease (2018) · cites this paper as [3]
In the citing paper
“Aβ accumulation activates the microglia and promotes pro-inflammatory mediators’ production and impairment of their phagocytic function (232, 233).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [232]
In the citing paper
“Colocalization of reactive microglia with Aβ deposits is a hallmark of AD pathology and has been reported also in brains from AD mouse models [102,103].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [102]
In the citing paper
“Proliferation and activation of microglia in the brain, around amyloid plaques, is a prominent characteristic of AD [102].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [102]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Microglia in Alzheimer's disease > Multifaceted immune activation
“the selective COX-2 inhibitor celecoxib was beneficial in slow decliners but harmful in the fast-progressing group.”
§ Microglia in Alzheimer's disease > Multifaceted immune activation
“Thus, COX-2 blockade in early phases may be harmful, whereas COX-1 inhibition (in addition to COX-2 inhibition) may be beneficial”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Microglia in Alzheimer's disease > Complement system
“blocking of C5a (124), a downstream component of the complement cascade, increased Aβ levels in the absence of increased Aβ production, reflecting the role of complement in microglial phagocytosis.In the same studies, complement blockade was associated with increased neurodegeneration.”
§ Microglia in Alzheimer's disease > References
“124. Fonseca MI, et al. Treatment with a C5aR antago- nist decreases pathology and enhances behavioral performance in murine models of Alzheimer's disease.”
Citations
Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Polazzi, E., Mengoni, I., Caprini, M., Peña‐Altamira, E., Kurtys, E., & Monti, B. (2012) · Neurosignals · doi:10.1159/000337115 · Cited by 9,023
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971 · cited 1×
“Microglial-derived immune factors can induce a so-called A1 astrocyte phenotype that contributes to neuronal death through reduced trophic support, impaired clearance capacity, and release of toxins (69).”
BackgroundThe chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189
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
2016 Alzheimer's disease facts and figures
Alzheimer's Association (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.001 · Cited by 5,069
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 · cited 1×
“Furthermore, while transcriptome studies have identified new markers selectively expressed on microglia, including the purinergic receptor P2Y12, transmembrane protein 119 (TMEM119), the chemokine receptor CX3CR1, and Siglec-H, other cell types may also display these markers (38, 39).”
Background
Research works printed but not linked: 1
- 10.1146/annurev-immunol-051116-052358 · DOI · Paper page
Cited by
Sorted by citations
Ageing as a risk factor for neurodegenerative disease
Hou, Y., Dan, X., Babbar, M., Wei, Y., Hasselbalch, S. G., Croteau, D. L., & Bohr, V. A. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0244-7 · Cited by 3,310
Knopman, D. S., Amieva, H., Petersen, R. C., Chételat, G., Holtzman, D. M., Hyman, B. T., Nixon, R. A., & Jones, D. T. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00269-y · Cited by 2,606
The Amyloid-β Pathway in Alzheimer’s Disease
Hampel, H., Hardy, J., Blennow, K., Chen, C., Perry, G., Kim, S. H., Villemagne, V. L., Aisen, P., Vendruscolo, M., Iwatsubo, T., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01249-0 · Cited by 1,952
Fang, E. F., Hou, Y., Palikaras, K., Adriaanse, B. A., Kerr, J. S., Yang, B., Lautrup, S., Hasan-Olive, M. M., Caponio, D., Dan, X., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0332-9 · Cited by 1,740
Microglia 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
Metadata
- Authors
- Sarlus, H., & Heneka, M. T.
- Affiliations
- University of Bonn (DE)
- Corresponding author
- Heneka, Michael T.
- Venue
- Journal of Clinical Investigation
- Published
- 2017-09-01
- Volume
- 127
- Issue
- 9
- Pages
- 3240-3249
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5669553
- OpenAlex
- W2750718695
- Semantic Scholar
- ef022dba477c27d3e9b6fce59a1f5267296be580
- Cited by
- 911
- References
- 162
- Citations by year
- 2026: 64 · 2025: 98 · 2024: 109 · 2023: 105 · 2022: 134 · 2021: 127 · 2020: 148 · 2019: 66 · 2018: 52 · 2017: 7
- FWCI
- 7.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- DZNE Pub (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- microglia, Alzheimer's disease, microglial activation, neuroinflammation, phagocytosis, neuroprotection, microglial receptors, neurodegeneration, brain homeostasis
- MeSH terms
- Alzheimer Disease, Animals, Brain, Central Nervous System, Complement System Proteins, Humans, Immune System, Inflammation, Macrophages, Phagocytosis, Cytokines, Microglia, Neurodegenerative Diseases, Cell Proliferation, Toll-Like Receptors, Mice
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).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
