The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index; 12 of the 24 sources its claims cite were checked for support.
CX3CR1 in Microglia Regulates Brain Amyloid Deposition through Selective Protofibrillar Amyloid-β Phagocytosis
Open accessAbstract
In Alzheimer's disease (AD), amyloid-β (Aβ) deposits are frequently surrounded by activated microglia but the precise role of these cells in disease progression remains unclear. The chemokine receptor CX3CR1 is selectively expressed in microglia and is thought to modulate their activity. To study the specific effects of microglia activation on amyloid pathology in vivo, we crossbred mice lacking CX3CR1 with the Alzheimer's mouse model CRND8. Surprisingly, we found that CX3CR1-deficient mice had lower brain levels of Aβ40 and Aβ42 and reduced amyloid deposits. Quantification of Aβ within microglia and time-lapse two-photon microscopy in live mice revealed that these cells were highly effective at the uptake of protofibrillar amyloid but were incapable of phagocytosis of fibrillar congophilic Aβ. CX3CR1 deletion was associated with increased phagocytic ability, which led to greater amyloid content within microglial phagolysosomes. Furthermore, CX3CR1-deficient mice had an increased number of microglia around individual plaques because of higher proliferative rates, which likely contributed to an overall greater phagocytic capacity. CX3CR1 deletion did not affect the degree of neuronal or synaptic damage around plaques despite increased microglia density. Our results demonstrate that microglia can regulate brain Aβ levels and plaque deposition via selective protofibrillar Aβ phagocytosis. Modulation of microglia activity and proliferation by CX3CR1 signaling may represent a therapeutic strategy for AD.
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Claims the paper makes
31 Own interpretation · 31 Own result · 12 Own method · 5 Partly supported · 5 No full text of the sources · 2 Supported · 2 Supported so far · 2 Not checked yet · 2 No basis given · 1 Couldn’t confirm · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Thus microglia may only be able to remove fibrillar amyloid from plaques during heightened levels of activation such as in injury models (DiCarlo et al., 2001) or after Aβ immunization (Bacskai et al., 2002).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > DISCUSSION
What the sources say
- Not matchedcites DiCarlo et al., 2001
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Partly supportedcites Bacskai et al., 2002 sourceExperimental — accuracy not yet measured
The introduction links microglial activation after topical antibody treatment to a possible Fc-mediated clearance mechanism, and the Results report clearance of some dense-core plaques after antibody treatment. But the paper does not establish that microglia themselves cleared those plaques or that heightened activation is required; it also finds evidence for non-Fc-mediated clearance. Its experiments used topical antibodies, not Aβ immunization. (LLM, conf=0.85)
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.
- Not matched
Every source the paper cites for this claim was checked and supports it.
In the paper
“Thus, CX3CR1 modulation of phagocytosis may involve the indirect effect of some proinflammatory cytokines which can attenuate phagocytosis (Koenigsknecht-Talboo and Landreth, 2005).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > DISCUSSION
What the sources say
- Supportedcites Koenigsknecht-Talboo and Landreth, 2005 source
The Results section ('Proinflammatory cytokines inhibit fAβ and opsonized zymosan-stimulated phagocytosis'; page unavailable) reports that proinflammatory agents inhibited those forms of phagocytosis, though immune IgG-mediated phagocytosis was unaffected. This supports the cited premise that some proinflammatory cytokines can attenuate phagocytosis; the CX3CR1 link is the citing authors’ proposed inference. (LLM, conf=0.90)
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.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Our findings support the concept that fractalkine through its receptor CX3CR1 (Harrison et al., 1998) acts as a repressor of microglia activation (Cardona et al., 2006).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > DISCUSSION
What the sources say
- Supportedcites Harrison et al., 1998 source
The Harrison et al. citation is attached to the phrase identifying CX3CR1 as fractalkine’s receptor; the separate Cardona et al. citation is attached to the claim about repressing microglial activation. Harrison et al.’s Results show that fractalkine-induced microglial responses were blocked by anti-CX3CR1 antibodies, supporting the part attributed to Harrison. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites Cardona et al., 2006 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.
- Rests on an assumption: CX3CR1 is specifically expressed in microglia in the brain.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, we found complete stability of the label at least over this 90 day interval (Figure 3B, C).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > RESULTS > Microglia are unable to phagocytose fibrillar congophilic amyloid in vivo
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.
- Rests on an assumption: Fluorescently labeled Aβ42 (HiLyte-555) behaves like endogenous Aβ42 in binding, stability, and phagocytosis.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Once bound to plaques, we found by time-lapse imaging that Aβ42 was highly stable over many weeks like we observed with methoxy-XO4.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > RESULTS > Microglia are unable to phagocytose fibrillar congophilic amyloid in vivo
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.
- Rests on an assumption: Fluorescently labeled Aβ42 (HiLyte-555) behaves like endogenous Aβ42 in binding, stability, and phagocytosis.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Microglia of each genotype represent ~50% of the total microglia population in these mixed cell cultures.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > MATERIALS AND METHODS > Microglia culture and in vitro phagocytosis assay
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, time-lapse TPM images over intervals of up to 1 month showed virtually no change in the size or shape of the original fluorescent plaque label (Figure 2A, B).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > RESULTS > Microglia are unable to phagocytose fibrillar congophilic amyloid in vivo
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.
- Rests on an assumption: In vivo two-photon imaging through a thinned skull does not alter microglial phagocytic behavior or plaque stability.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At 2 months of age, both CRND8/CX3CR1−/− mice and their wild-type littermates (CRND8/CX3CR1+/+) demonstrated low levels of total brain Aβ40 and Aβ42 peptides (Figures 1A, B).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > RESULTS > CX3CR1 deficiency in microglia leads to reduced brain β-amyloid load and deposition
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.
- Rests on an assumption: The CRND8 mouse model of amyloid deposition is relevant to human Alzheimer's disease.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“reduced amyloid deposits”
- Also stated in: § CX3CR1 deficiency in microglia leads to reduced brain β-amyloid load and deposition · plain
“We found that CRND8/CX3CR1−/− mice had a significantly reduced number of amyloid plaques at both 3 and 5 months of age (Figure 1C, D).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > 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: passes — The paper gives a reason why it holds.
- Rests on an assumption: The CRND8 mouse model of amyloid deposition is relevant to human Alzheimer's disease.
- Also stated in: § CX3CR1 deficiency in microglia leads to reduced brain β-amyloid load and deposition · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, CX3CR1 deficient mice had an increased number of microglia around individual plaques due to higher proliferative rates, which likely contributed to an overall greater phagocytic capacity.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > Abstract
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. 20
- Probably not a substantial claim. 16
Every source the paper cites for this claim was checked and supports it.
In the paper
“The chemokine receptor CX3CR1 is selectively expressed in microglia and is thought to modulate their activity.”
- Also stated in: § INTRODUCTION · plain
“In the brain, this receptor is exclusively expressed in microglia and selectively modulates microglial activity in response to its ligand the chemokine fractalkine (Harrison et al., 1998).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > Abstract
What the sources say
- Supportedcites Harrison et al., 1998 source
The Results identify microglia as the source of CX3CR1 expression in the examined brain tissue and show that fractalkine induces CX3CR1-dependent chemotaxis and calcium signaling in cultured microglia. The Discussion describes microglia as the principal fractalkine-responding cells in the CNS, supporting the claim in that context. (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.
- Also stated in: § INTRODUCTION · plain
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Microglia have been shown to be capable of phagocytosis of amyloid fibrils (2)”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > INTRODUCTION
What the sources say
- Could not verifycites [2] sourceExperimental — accuracy not yet measured
The Results and Discussion passages address neutrophil chemokine receptors and migration during sepsis, not microglia or amyloid fibrils. Searches for microglial phagocytosis and amyloid-fibril uptake found no passage in our copy addressing the claim. (LLM, conf=0.76)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Could not verify
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Conflicting evidence in the literature suggests either neurotoxic or neuroprotective effects of CX3CR1 deletion in various disease models (Cardona et al., 2006; Fuhrmann et al., 2010).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites Cardona et al., 2006 source
- Supportedcites Fuhrmann et al., 2010 source
The paper reports that Cx3cr1 knockout prevented neuron loss in its Alzheimer’s disease mouse model. It also states that under other neuroinflammatory conditions, knockout has been reported to increase or decrease neurotoxicity, supporting the citing sentence’s description of conflicting evidence (passage [1], labeled Abstract). (LLM, conf=0.93)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Previous in vivo results range from showing that microglia are effective at phagocytosis of fibrillar amyloid (Frautschy et al., 1991; Bacskai et al., 2002; Bolmont et al., 2008) to suggesting that microglia play no role in the control of amyloid deposition (Grathwohl et al., 2009).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > INTRODUCTION
What the sources say
- Could not verifycites Frautschy et al., 1991 sourceExperimental — accuracy not yet measured
The indexed Abstract describes neuronal responses to amyloid cores injected into rat brain, but does not report microglial phagocytosis. Searches for microglia and phagocytosis returned only the abstract and references; the available indexed text does not establish the finding attributed to Frautschy et al. (LLM, conf=0.72)
- Partly supportedcites Bacskai et al., 2002 sourceExperimental — accuracy not yet measured
The Results report in vivo clearance of dense-core amyloid plaques after antibody treatment, and the Discussion treats microglial phagocytosis as a possible clearance mechanism. But the paper attributes direct evidence of microglial phagocytosis to ex vivo work; its own in vivo experiments also found effective Fc-independent clearance. It therefore does not show that microglia phagocytosed fibrillar amyloid in vivo. (LLM, conf=0.86)
- Supportedcites Grathwohl et al., 2009 source
The Introduction reports that substantially reducing or nearly eliminating microglia did not alter amyloid plaque load in two APP transgenic mouse models over 2–4 weeks. It concludes that, in those models, de novo formation and progression of cerebral amyloidosis are controlled by nonmicroglial factors or cells. This supports the citing sentence’s characterization as a suggestion, within the study’s mouse-model and time-frame limits. (LLM, conf=0.91)
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.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Thus, the long-term persistence of methoxy-XO4 and Aβ42 (HiLyte)-555 plaque labeling coupled with the absence of TS label inside microglia strongly suggests that little phagocytosis of fibrillar amyloid takes place in vivo.”
- Also stated in: § Microglia are effective at phagocytosis of protofibrillar amyloid in vivo · hedged
“Together, these data indicate that microglia exhibit an increasing capacity for Aβ phagocytosis as it gradually adopts protofibrillar conformations but fail to phagocytose fibrillar deposits that have adopted a β-pleated sheet conformation.”
- Also stated in: § DISCUSSION · plain
“However, in contrast to recent imaging studies (Bolmont et al., 2008) we found that microglia, while highly effective at phagocytosis of oligomeric and protofibrillar Aβ, were incapable of removing fibrillar amyloid from preexisting plaques in vivo.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > RESULTS > Microglia are unable to phagocytose fibrillar congophilic amyloid in vivo
What the sources say
- Partly supportedcites Bolmont et al., 2008 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) proposes that microglia may phagocytose protofibrils at plaque edges, but does not report increasing phagocytic capacity as Aβ changes conformation. It also says further study is needed to determine whether the material taken up is soluble or fibrillar Aβ, so it does not establish that microglia fail to phagocytose fibrillar deposits in vivo. (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.
- Also stated in: § Microglia are effective at phagocytosis of protofibrillar amyloid in vivo · hedged
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“it remains unclear to what extent microglia are capable of removing amyloid from pre-existing fibrillar congophilic plaques (Stalder et al., 2001) or of preventing the deposition of smaller protofibrillar Aβ aggregates (Grathwohl et al., 2009).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites Stalder et al., 2001 source
- Partly supportedcites Grathwohl et al., 2009 sourceExperimental — accuracy not yet measured
The citation to Grathwohl et al. attaches to the claim about preventing deposition of smaller protofibrillar Aβ aggregates, not to the preceding claim about removing pre-existing plaques. In the Introduction (page unavailable), the paper reports that microglial ablation did not prevent plaque formation or change the extent of Aβ deposition in APP mouse models. It does not specifically assess smaller protofibrillar aggregates, so it supports the broader uncertainty about microglia and deposition but not that specific form. (LLM, conf=0.82)
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.
Probably not a substantial claim. It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We obtained high resolution confocal images of brain slices from CRND8 mice stained with A11 and 4G8 antibodies, which detect oligomeric and other protofibrillar conformations respectively (Lesné et al., 2006; Kayed et al., 2007).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > RESULTS > Microglia are effective at phagocytosis of protofibrillar amyloid in vivo
What the sources say
- Not checked — no full text of the sourcecites Lesné et al., 2006 source
- Partly supportedcites Kayed et al., 2007 sourceExperimental — accuracy not yet measured
The Background and Results (pages not provided) support A11 as a detector of prefibrillar oligomers. But the Results report that 4G8 reacts with both fibrillar and prefibrillar samples, including monomer-sized material; they do not support describing it as a detector of a distinct protofibrillar conformation. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“there was no significant difference in amyloid precursor protein (APP) concentrations (Figure 1E), mRNA expression of APP processing enzymes (BACE1 and 2; PS1 and 2) (Figure 1F) or levels of APP cleavage products (Figure 1G).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > RESULTS > CX3CR1 deficiency in microglia leads to reduced brain β-amyloid load and deposition
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.
- Rests on an assumption: The CRND8 mouse model of amyloid deposition is relevant to human Alzheimer's disease.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Microglia cell bodies however, can remain stable over months (Supplementary figure 4) but no significant difference in stability between mice of different CX3CR1 genotypes was observed (Figures 7E, F).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > RESULTS > CX3CR1 deficiency is associated with increased microglia proliferation and clustering around fibrillar amyloid plaques
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We show that deletion of the fractalkine receptor CX3CR1, which in the brain is specifically expressed in microglia, leads to a significant reduction in the total levels of brain Aβ and in the number of amyloid plaques in a mouse model of AD.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > DISCUSSION
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.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interestingly, we found that the overall proportion of microglia that were BrdU-labeled was significantly greater in CRND8/CX3CR1−/− mice than in CRND8/CX3CR1+/+ littermates (Figure 7C, D), while non-plaque areas showed substantially lower overall proliferation rates and no significant differences between genotypes (Figure 7D).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > RESULTS > CX3CR1 deficiency is associated with increased microglia proliferation and clustering around fibrillar amyloid plaques
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pre incubation with anti-CX3CR1 neutralizing antibody 2 hours prior to the phagocytosis assay led to increased microsphere phagocytosis in CX3CR1+/+ microglia but not those lacking CX3CR1 (Figure 6E) demonstrating rapid and specific modulation of phagocytosis by the reduction of CX3CR1 activity.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > RESULTS > CX3CR1 deficient microglia have an enhanced capacity for Aβ phagocytosis
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.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Results were validated by manual counting in a subset of stacks.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > MATERIALS AND METHODS > Quantification of microglia, neuron and synapse density around plaques
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Microglia density around plaques was quantified in blindly selected plaques of the same average size to eliminate size as a variable which can lead to differences in microglia number unrelated to the CX3CR1 genotype..”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > MATERIALS AND METHODS > Quantification of microglia, neuron and synapse density around plaques
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
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
“Thus, it is not clear how or to what extent microglia control brain amyloid levels or deposition.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > INTRODUCTION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“CX3CR1 deletion was associated with increased phagocytic ability which led to greater amyloid content within microglial phagolysosomes.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > 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.
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, our data demonstrate that microglia play an important role in selective phagocytosis of oligomeric and protofibrillar Aβ but not of preexisting congophilic amyloid plaques.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > INTRODUCTION
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.
It may state two separate claims as one.
- Rests on an assumption: The absence of intracellular Thioflavin-S labeling indicates lack of phagocytosis of fibrillar amyloid rather than rapid degradation or masking of the label.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All images were obtained with standardized parameters of laser intensity, gain and pinhole size.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > MATERIALS AND METHODS > Quantification of infused fluor-Aβ42 phagocytosis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
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
“CX3CR1 deletion increased microglia proliferation and numbers specifically around plaques, which coupled with their increased phagocytic ability, resulted in decreased brain amyloid levels and deposition.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > INTRODUCTION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus IBA1 labels all brain microglia but cannot differentiate them from infiltrating macrophages given that macrophages also label with IBA1.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > MATERIALS AND METHODS > Quantification of microglia, neuron and synapse density around plaques
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All other experiments including quantification of Aβ within microglia and in vivo imaging experiments were done in mixed gender mice but with equal gender distribution on each experimental group.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > MATERIALS AND METHODS > Mice
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A subset of images was counted manually by an unbiased individual to corroborate the accuracy of our automated counting.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > MATERIALS AND METHODS > Quantification of Thioflavin-S labeled Amyloid Plaques
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Confocal images of plaques selected for their similar size, location and cortical layer were obtained for quantitative imaging using an Olympus FV10i Confocal Microscope (60X objective N.A. 1.2). Image z-stacks were taken with standardized laser intensity, gain and pinhole sizes to allow inter-animal comparisons.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > MATERIALS AND METHODS > Quantification of 4G8 and A11 fluorescence inside microglia phagolysosomes
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
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
“Increased fractalkine signaling in aging could in theory restrain microglia and predispose individuals to amyloid deposition and toxicity.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > DISCUSSION
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.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“However, technical limitations of in vivo imaging make it unfeasible to quantify microglia cell body dynamics over longer intervals with sufficient precision.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > RESULTS > CX3CR1 deficiency is associated with increased microglia proliferation and clustering around fibrillar amyloid plaques
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
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
“Ablation is likely to induce marked astrocyte activation and could turn these cells into much more effective phagocytes which could compensate for the loss of microglia and thus explain the apparent lack of effect of microglia ablation on Aβ levels.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: 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
“Ongoing microglial phagocytosis around growing fibrillar deposits could reduce levels of oligomeric and protofibrillar Aβ, which may change the equilibrium between monomers, oligomers and fibrils, altering the process of nucleation-dependent polymerization that leads to fibrillar plaque formation (Harper and Lansbury Jr., 1997; Walsh et al., 1999).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Harper and Lansbury Jr., 1997 source
- Not matchedcites Walsh et al., 1999
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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
“Thus it appears that microglia activation is not an all or none process and its net effect may depend on the particular pathological scenario (Hanisch and Kettenmann, 2007).”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Hanisch and Kettenmann, 2007 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.
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 we cannot rule out that subtle variations in microglia recruitment/retention could contribute to the observed disparities in microglia number around plaques.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > RESULTS > CX3CR1 deficiency is associated with increased microglia proliferation and clustering around fibrillar amyloid plaques
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.
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 it appears that CX3CR1 deficiency has neither neuroprotective nor neurotoxic effects around individual plaques at least in this model of Alzheimer’s-like pathology.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > RESULTS > CX3CR1 deletion does not affect the degree of neuronal or synaptic injury around amyloid plaques
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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, it is likely that the main role played by microglia is to ameliorate the formation of new fibrillar plaques rather than to remove preexisting ones, with the most critical effect likely being at the earliest stages of plaque deposition.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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 we cannot rule out that some of the effects we observed are at least partly due to peripheral macrophages entering the brain.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > DISCUSSION
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.
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 effect of CX3CR1 deletion on brain amyloid was mediated by a general enhancement of microglia phagocytic ability as demonstrated both in vitro and in vivo.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > DISCUSSION
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.
It may state two separate claims as one.
- The authors state this as an assumption: The disparity in Aβ uptake between CX3CR1 genotypes is mostly due to differential phagocytic capacity rather than macropinocytosis.
- Rests on an assumption: CX3CR1 is specifically expressed in microglia in the brain.
The paper relies on this without support.
The CRND8 mouse model of amyloid deposition is relevant to human Alzheimer's disease.
“we crossbred mice lacking CX3CR1 with the Alzheimer’s mouse model CRND8”
“CX3CR1−/− mice were crossbred with transgenic mice (CRND8) harboring the human amyloid precursor protein gene with the Indiana and Swedish mutations (Chishti et al., 2001).”
The paper relies on this without support.
Fluorescently labeled Aβ42 (HiLyte-555) behaves like endogenous Aβ42 in binding, stability, and phagocytosis.
“we developed a method for subarachnoid infusion of fluorescently tagged Aβ peptides”
“Aβ42 (HiLyte)-555 was being infused”
The paper relies on this without support.
In vivo two-photon imaging through a thinned skull does not alter microglial phagocytic behavior or plaque stability.
“GFP-labeled microglia and Methoxy-X04 (MX04) labeled plaques were imaged through a thinned skull preparation as previously described (Grutzendler et al., 2002).”
The paper relies on this without support.
The absence of intracellular Thioflavin-S labeling indicates lack of phagocytosis of fibrillar amyloid rather than rapid degradation or masking of the label.
“Quantification of TS fluorescence within IBA1-immunolabeled cells revealed absence of any intracellular TS labeling (Figure 2C, D) regardless of the CX3CR1 genotype (Figure 2D).”
“we found complete stability of the label at least over this 90 day interval (Figure 3B, C).”
The authors state this as an assumption.
The disparity in Aβ uptake between CX3CR1 genotypes is mostly due to differential phagocytic capacity rather than macropinocytosis.
“However, given that CX3CR1 deletion is able to modulate phagocytosis of polystyrene microspheres, we assume that the disparity in Aβ uptake between genotypes is mostly due to differential phagocytic capacity rather than macropinocytosis.”
The paper relies on this without support.
CX3CR1 is specifically expressed in microglia in the brain.
“We show that deletion of the fractalkine receptor CX3CR1, which in the brain is specifically expressed in microglia, leads to a significant reduction in the total levels of brain Aβ and in the number of amyloid plaques in a mouse model of AD.”
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
“Microglia engulf and degrade Aβ74,75”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [74]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“These studies provided important insight on the role of CX3CR1 in AD and suggested that targeting CX3CR1 activity may be a therapeutic strategy to lower Aβ levels.”
From Heterozygous CX3CR1 Deficiency in Microglia Restores Neuronal β-Amyloid Clearance Pathways and Slows Progression of Alzheimer's Like-Disease in PS1-APP Mice (2019) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“In Alzheimer's disease complete deletion of CX3CR1 in models of amyloid deposition reduced Aβ deposits and enhanced microglial Aβ phagocytic ability (16, 17).”
From Heterozygous CX3CR1 Deficiency in Microglia Restores Neuronal β-Amyloid Clearance Pathways and Slows Progression of Alzheimer's Like-Disease in PS1-APP Mice (2019) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“Complete deletion of CX3CR1 in models of amyloid deposition have been shown to reduce Aβ deposits and enhanced microglial Aβ phagocytosis (16, 17).”
From Heterozygous CX3CR1 Deficiency in Microglia Restores Neuronal β-Amyloid Clearance Pathways and Slows Progression of Alzheimer's Like-Disease in PS1-APP Mice (2019) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“although it is important to note that the efficiency of individual phagocytic processes can be dependent on experimental conditions65–67.”
From Transcriptional signature in microglia associated with Aβ plaque phagocytosis (2021) · cites this paper as [67]
In the citing paper
“Deletion of CX3CR1 or depression of the CX3CL1/CX3CR1 axis reduces Aβ deposition [130–132] but exacerbates tau pathology, such as increased phosphorylation and aggregation of tau, and this is associated with worsened behavioral and cognitive impairments [132–137] (Fig. 1).”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [130]
In the citing paper
“whereas a reduction in plaque load was observed with Cx3cr1 knockout in amyloid models (Lee et al., 2010; Liu et al., 2010)”
From Microglia in Alzheimer’s disease (2018) · cites this paper as Liu et al., 2010
In the citing paper
“In AD, microglia cluster around beta-amyloid plaques highlighting their inability to clear beta-amyloid (Hickman et al., 2008; Liu et al., 2010).”
From iPSC-derived human microglia-like cells to study neurological diseases (2017) · cites this paper as Liu et al., 2010
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
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > MATERIALS AND METHODS > Quantification of microglia, neuron and synapse density around plaques
“Then, 10 donut-shaped selection bands of 3 μm width were created at 3 μm intervals, covering a 30 μm circular area out from the evened plaque edge.”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > MATERIALS AND METHODS > Quantification of microglia, neuron and synapse density around plaques
“with the first band nearly adjacent to the plaque (all pixels 2–5 μm from the thresholded plaque edge), and the last band about 30 um away from the plaque edge (all pixels 32–35 μm from the thresholded plaque edge).”
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
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > MATERIALS AND METHODS > Microglia culture and in vitro phagocytosis assay
“pretreated with or without 10μg/ml CX3CR1 neutralizing antibody for 30min and then incubated for 2 hours”
§ CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis > RESULTS > CX3CR1 deficient microglia have an enhanced capacity for Aβ phagocytosis
“Pre incubation with anti-CX3CR1 neutralizing antibody 2 hours prior to the phagocytosis assay”
Cited works that were retracted
Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
In the paper
“We obtained high-resolution confocal images of brain slices from CRND8 mice stained with A11 and 4G8 antibodies, which detect oligomeric and other protofibrillar conformations, respectively (Lesné et al., 2006; Kayed et al., 2007).”
Cited work 10.1038/nature04533 · retracted 2024-06-24 · notice 10.1038/s41586-024-07691-8 · this paper published 2010-12-15
Citations
Cites
1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769 · cited 2×
“We obtained high-resolution confocal images of brain slices from CRND8 mice stained with A11 and 4G8 antibodies, which detect oligomeric and other protofibrillar conformations, respectively (Lesné et al., 2006; Kayed et al., 2007).”
MethodRetractedMicroglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110 · cited 4×
“Microglia have been shown to exacerbate neuronal death mainly in acute and subacute injury models in which they are fully activated (Wu et al., 2000; Cardona et al., 2006; Block et al., 2007).”
BackgroundResultInfluentialATP mediates rapid microglial response to local brain injury in vivo
Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., Littman, D. R., Dustin, M. L., & Gan, W.-B. (2005) · Nature Neuroscience · doi:10.1038/nn1472 · Cited by 3,913 · cited 1×
“Microglia are the resident immune cells of the brain and can become activated by a variety of changes in its structural and biochemical integrity (Davalos et al., 2005; Hanisch and Kettenmann, 2007).”
BackgroundSelf-citationMicroglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676 · cited 2×
“Thus, it appears that microglia activation is not an all-or-none process and its net effect may depend on the particular pathological scenario (Hanisch and Kettenmann, 2007).”
BackgroundDiffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506 · cited 3×
“This function may be critical in controlling A deposition as well as levels of potentially neurotoxic A oligomers (Lambert et al., 1998).”
BackgroundJung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632 · cited 2×
“To address these questions, we investigated mice lacking the chemokine receptor CX3CR1 (Jung et al., 2000).”
BackgroundHarper, J. D., & Lansbury, P. T. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.385 · Cited by 1,652
Local self-renewal can sustain CNS microglia maintenance and function throughout adult life
Ajami, B., Bennett, J. L., Krieger, C., Tetzlaff, W., & Rossi, F. M. V. (2007) · Nature Neuroscience · doi:10.1038/nn2014 · Cited by 1,643 · cited 2×
“Although currently it is thought that macrophages may normally not enter the brain in significant numbers in the absence of blood– brain barrier disruption (Ajami et al., 2007; Mildner et al., 2007), fractalkine/CX3CR1 signaling may also have chemotactic effects on macrophages (Imai et al., 1997).”
BackgroundControl of microglial neurotoxicity by the fractalkine receptor
Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., Huang, D., Kidd, G., Dombrowski, S., Dutta, R., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1715 · Cited by 1,531 · cited 6×
“Microglia have been shown to exacerbate neuronal death mainly in acute and subacute injury models in which they are fully activated (Wu et al., 2000; Cardona et al., 2006; Block et al., 2007).”
BackgroundInfluentialImai, T., Hieshima, K., Haskell, C. A., Baba, M., Nagira, M., Nishimura, M., Kakizaki, M., Takagi, S., Nomiyama, H., Schall, T. J., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80438-9 · Cited by 1,472 · cited 2×
“, 2007), fractalkine/CX3CR1 signaling may also have chemotactic effects on macrophages (Imai et al., 1997).”
Background
Cited by
Sorted by citations
Microglia in Alzheimer’s disease
Hansen, D. V., Hanson, J. E., & Sheng, M. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201709069 · Cited by 1,935
Microglia in neurodegeneration
Hickman, S., Izzy, S., Sen, P., Morsett, L., & El Khoury, J. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0242-x · Cited by 1,710
Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration
Deczkowska, A., Keren-Shaul, H., Weiner, A., Colonna, M., Schwartz, M., & Amit, I. (2018) · Cell · doi:10.1016/j.cell.2018.05.003 · Cited by 1,474
iPSC-derived human microglia-like cells to study neurological diseases
Abud, E. M., Ramirez, R. N., Martinez, E. S., Healy, L. M., Nguyen, C. H. H., Newman, S. A., Yeromin, A. V., Scarfone, V. M., Marsh, S. E., Fimbres, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.03.042 · Cited by 1,154
“In AD, microglia cluster around beta-amyloid plaques highlighting their inability to clear beta-amyloid (Hickman et al., 2008, Liu et al., 2010).”
Microglia development and function
Nayak, D., Roth, T. L., & McGavern, D. B. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120240 · Cited by 1,154
Innate immunity in the central nervous system
Ransohoff, R. M., & Brown, M. A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci58644 · Cited by 1,034
“CX3CR1-deficient CX3CR1-deficient mice show enhanced amyloid clearance in Alzheimer’s disease (AD) amyloid deposition models (64), consistent with beneficial activation of microglia (52, 63, 65, 66).”
Microglia-mediated neuroinflammation in neurodegenerative diseases
Subhramanyam, C. S., Wang, C., Hu, Q., & Dheen, S. T. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.004 · Cited by 897
Yuan, P., Condello, C., Keene, C. D., Wang, Y., Bird, T. D., Paul, S. M., Luo, W., Colonna, M., Baddeley, D., & Grutzendler, J. (2016) · Neuron · doi:10.1016/j.neuron.2016.05.003 · Cited by 817
“However, multiple recent lines of evidence indicate that microglia are ineffective at removing fibrillar Ab in vivo (Condello et al., 2011; Liu et al., 2010; Stalder et al., 2001).”
Self-citationMicroglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques
Condello, C., Yuan, P., Schain, A., & Grutzendler, J. (2015) · Nature Communications · doi:10.1038/ncomms7176 · Cited by 718
Self-citationHeterogeneity of CNS myeloid cells and their roles in neurodegeneration
Prinz, M., Priller, J., Sisodia, S. S., & Ransohoff, R. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2923 · Cited by 674
CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity
Rogers, J. T., Morganti, J. M., Bachstetter, A. D., Hudson, C. E., Peters, M. M., Grimmig, B. A., Weeber, E. J., Bickford, P. C., & Gemma, C. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3667-11.2011 · Cited by 624
“Furthermore, CX3CR1 / mice crossed with the AD mouse model CRND8 had lower brain levels of A 40 and A 42 and reduced amyloid deposits, which are related to increased microglia proliferation and phagocytosis (Liu et al., 2010).”
BackgroundJanus-faced microglia: beneficial and detrimental consequences of microglial phagocytosis
Sierra, A., Abiega, O., Shahraz, A., & Neumann, H. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00006 · Cited by 574
“The fractalkine receptor, a regulator of phagocytosis, has been found to contribute to the Aβ burden by some (Lee et al., 2010; Liu et al., 2010) but not others (Fuhrmann et al., 2010).”
BackgroundAmyloid-β-independent regulators of tau pathology in Alzheimer disease
van der Kant, R., Goldstein, L. S. B., & Ossenkoppele, R. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0240-3 · Cited by 580
Inflammation: the link between comorbidities, genetics, and Alzheimer’s disease
Newcombe, E. A., Camats-Perna, J., Silva, M. L., Valmas, N., Huat, T. J., & Medeiros, R. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1313-3 · Cited by 532
Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation
Chen, Y., & Yu, Y. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02853-3 · Cited by 516
Krabbe, G., Halle, A., Matyash, V., Rinnenthal, J. L., Eom, G. D., Bernhardt, U., Miller, K. R., Prokop, S., Kettenmann, H., & Heppner, F. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060921 · Cited by 478
Bidirectional Microglia–Neuron Communication in Health and Disease
Szepesi, Z., Manouchehrian, O., Bachiller, S., & Deierborg, T. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00323 · Cited by 459
“However, others have demonstrated that both APP-PS1/CX3CR1−/− and CRND8/CX3CR1−/− mice showed reduction in Aβ deposition with increased number of microglia (Lee et al., 2010; Liu et al., 2010).”
BackgroundThe contribution of neuroinflammation to amyloid toxicity in Alzheimer's disease
Minter, M. R., Taylor, J. M., & Crack, P. J. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13411 · Cited by 451
“CX3CR1 deficiency in multiple mouse models of AD has been shown to promote microglial phagocytosis of Ab, reducing plaque burden and neurotoxicity (Fuhrmann et al. 2010; Lee et al. 2010; Liu et al. 2010).”
BackgroundLucin, K. M., O’Brien, C. E., Bieri, G., Czirr, E., Mosher, K. I., Abbey, R. J., Mastroeni, D. F., Rogers, J., Spencer, B., Masliah, E., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.046 · Cited by 374
Factors regulating microglia activation
Kierdorf, K., & Prinz, M. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00044 · Cited by 360
“Nevertheless, several studies on the role of CX3CR1deficiency in animal models for Alzheimer’s disease (AD) revealed quite divergent results (Fuhrmann et al., 2010; Lee et al., 2010; Liu et al., 2010; Prinz et al., 2011).”
ResultTranscriptional signature in microglia associated with Aβ plaque phagocytosis
Grubman, A., Choo, X. Y., Chew, G., Ouyang, J. F., Sun, G., Croft, N. P., Rossello, F. J., Simmons, R., Buckberry, S., Landin, D. V., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23111-1 · Cited by 357
Macrophages: An Inflammatory Link Between Angiogenesis and Lymphangiogenesis
Corliss, B. A., Azimi, M. S., Munson, J. M., Peirce, S. M., & Murfee, W. L. (2016) · Microcirculation · doi:10.1111/micc.12259 · Cited by 356
“A limitation with this approach, however, is that the radiation used to deplete stem cells in the bone marrow also inflicts whole body injury, causing increased vascular permeability [68,140] and other nonphysiologic behaviors [146,169].”
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BackgroundMicroglia, seen from the CX3CR1 angle
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“…the CX3CR1−/− mice to CRND8 transgenic mice that harbor a gene encoding a mutant human amyloid precursor protein also resulted in reduced Aβ deposits, with the CX3CR1deficient microglia phagocytosing amyloid plaques and displaying higher proliferation rates in the plaque regions (Liu et al., 2010).”
BackgroundMicroglia in Health and Disease
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Advances in developing novel therapeutic strategies for Alzheimer’s disease
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“Genetic deletion of the chemokine receptor CX3CR1 in microglia can also enhance formation of microglial barrier around amyloid plaques [212], and thereby reduce plaque load [214, 215].”
BackgroundTissue-specific Role of CX3CR1 Expressing Immune Cells and Their Relationships with Human Disease
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“In the brain, CX3CL1/CX3CR1 signaling can modulate the production of cytokines by microglia cells (8).”
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“Notably, despite the increased density of microglia, there was no effect of CX3CR1 deletion on the degree of neuronal and synaptic damage surrounding the plaques [93].”
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“Whether internalized Ab aggregates are degraded remains uncertain but many evidence support the capacity of monocytes/macrophages to eliminate Ab with much greater efficiency than microglia (Fiala et al., 2007; Liu et al., 2010; Majumdar et al., 2008; 2007; Simard et al., 2006).”
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“28 days Yes ↓ Aβ deposition, ↑ Aβ phagocytosis, ↑ microglia proliferation, = neuronal injury (198)”
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“It has been reported that microglia can take up and degrade fibrillary Ab by phagocytosis (Cho et al., 2014; Liu et al., 2010).”
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“On the other hand, microglial responses to plaques may contribute to stabilizing plaque size, which remains relatively stable throughout the clinical course of the disease (22, 33), perhaps by effectively phagocytosing and degrading the smaller and more soluble AA species in the halo around dense-core plaques (59).”
Microglia contribute to the propagation of Aβ into unaffected brain tissue
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“In Alzheimer’s disease (AD), CX3CL1/CX3CR1 blockade modulates microglia phagocytic activity in a way that markedly attenuates amyloid deposition (Lee et al., 2010; Liu et al., 2010).”
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“Consistently, CX3CR1 receptor deficiency was previously shown to increase TAU phosphorylation [141] and to ameliorate Aβ levels and deposition [142, 143].”
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“, 2011), and amyloid plaque clearance in Alzheimer’s disease models (Lee et al., 2010; Liu et al., 2010).”
BackgroundCX3CL1/CX3CR1 signaling targets for the treatment of neurodegenerative diseases
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CX3CL1 Is Neuroprotective in Permanent Focal Cerebral Ischemia in Rodents
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“In different models of neuroinflammatory diseases, CX3CR1 deficiency correlated with enhanced microglia phagocytosis (Lee et al., 2010; Liu et al., 2010) and altered production of inflammatory cytokines (Cardona et al.”
BackgroundSex differences in microglial CX3CR1 signalling determine obesity susceptibility in mice
Dorfman, M. D., Krull, J. E., Douglass, J. D., Fasnacht, R. D., Lara-Lince, F., Meek, T. H., Shi, X., Damian, V. M., Hồng, N. T., Matsen, M. E., et al. (2017) · Nature Communications · doi:10.1038/ncomms14556 · Cited by 175
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“Several studies proposed that microglia/macrophages are involved in the clearance of A b (Rogers et al , 2002; Simard et al , 2006; El Khoury et al , 2007; Bolmont et al , 2008; Lee & Landreth, 2010; Liu et al , 2010; Krabbe et al , 2013).”
Functions of microglia in the central nervous system—beyond the immune response
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“affecting the integrity of the BBB [19,20], decreasing tight junction proteins [21] and inducing endothelial cell apoptosis [22].”
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Systematic Review of the Neurobiological Relevance of Chemokines to Psychiatric Disorders
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Clearance of Amyloid-β Peptides By Microglia and Macrophages: the Issue of What, When and Where
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TREM2 Function in Alzheimer’s Disease and Neurodegeneration
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Microglia limit the expansion of β-amyloid plaques in a mouse model of Alzheimer’s disease
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“Beta amyloid [29] and Tau protiens [30]—whose accu-”
BackgroundCXCR3 promotes plaque formation and behavioral deficits in an Alzheimer’s disease model
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“Interestingly, from the Cx3cr1−/− studies described above, one may predict that the FKN over expression may worsen amyloid pathology [7, 9, 68].”
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“The switch from a pro-resolution phenotype to a hypophagocytic phenotype was suggested to represent a proinflammatory state that occurs when the microglia fail to digest and degrade engulfed, highly stable filamentous protein aggregates ( 45 , 46 ).”
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Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging
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“However, these microglial processes are not optimally positioned to remove prefibrillar Ab because they are closely anchored to the perimeter of the compact plaque core (27) rather than at the site of the less compact plaque halo and under normal conditions have been shown to have a limited capacity for phagocytosis o…”
InfluentialSelf-citationCellular Stress Response and Immune Signaling in Retinal Ischemia–Reperfusion Injury
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“As is seen in the case of Alzheimer’s, where the activation of microglia helps in clearance of amyloid load and hence is beneficial (61, 62).”
BackgroundOpposing Effects of Membrane-Anchored CX3CL1 on Amyloid and Tau Pathologies via the p38 MAPK Pathway
Lee, S., Xu, G., Jay, T. R., Bhatta, S., Kim, K.-W., Jung, S., Landreth, G. E., Ransohoff, R. M., & Lamb, B. T. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0853-14.2014 · Cited by 123
“In several transgenic mouse models of AD, CX3CR1 deficiency ameliorated A deposition by altering microglial activation and promoting microglial phagocytosis (Lee et al., 2010; Liu et al., 2010).”
BackgroundModulation of inflammation in transgenic models of Alzheimer’s disease
Birch, A. M., Katsouri, L., & Sastre, M. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-25 · Cited by 121
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Inflammatory mechanisms in neurodegeneration
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“Grutzendler and colleagues demonstrated in an in vivo study that microglia were highly effective at protofibrillar Ab uptake but were incapable of phagocytosis of fibrillar congophilic Ab (Liu et al. 2010).”
BackgroundLee, D. C., Ruiz, C. R., Lebson, L. A., Selenica, M. B., Rizer, J., Hunt, J. B., Rojiani, R., Reid, P., Kammath, S., Nash, K. R., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.014 · Cited by 122
“…on amyloid versus tau pathology is being observed, with microglial activation by lipopolysaccharide, fractalkine receptor deletion, or IL-1 overexpression benefiting amyloid pathology, yet exacerbating tau pathology (DiCarlo et al., 2001; Lee et al., 2010; Liu et al., 2010; Shaftel et al., 2007).”
Eles, J. R., Vazquez, A. L., Snyder, N. R., Lagenaur, C. F., Murphy, M. C., Kozai, T. D. Y., & Cui, X. T. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.10.054 · Cited by 117
Genetic targeting of microglia
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Fractalkine in the nervous system: neuroprotective or neurotoxic molecule?
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Attenuation of β-Amyloid Deposition and Neurotoxicity by Chemogenetic Modulation of Neural Activity
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“Given that small plaques and diffuse plaques are likely to be the most recently formed (Liu et al., 2010; Condello et al., 2011), these data suggest that neural activity significantly influences the formation of new plaques but does not Figure 3.”
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Reduced microglial CX3CR1 expression delays neurofibromatosis‐1 glioma formation
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Time-dependent effects of CX3CR1 in a mouse model of mild traumatic brain injury
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In vivo dynamics of innate immune sentinels in the CNS
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Cytokine-producing microglia have an altered beta-amyloid load in aged APP/PS1 Tg mice
Babcock, A. A., Ilkjær, L., Clausen, B. H., Villadsen, B., Dissing-Olesen, L., Bendixen, A. T. M., Lyck, L., Lambertsen, K. L., & Finsen, B. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.03.006 · Cited by 107
G Protein-Coupled Receptors (GPCRs) in Alzheimer’s Disease: A Focus on BACE1 Related GPCRs
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“AD is the most common neurodegenerative disorder afflicting around 24.0 million people worldwide, the morbidity rate of which rises dramatically as people get older (Erb et al., 2015).”
InfluentialHernandez, M. X., Jiang, S., Cole, T. A., Chu, S., Fonseca, M. I., Fang, M. J., Hohsfield, L. A., Torres, M. D., Green, K. N., Wetsel, R. A., et al. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0210-z · Cited by 104
Cx3cr1- deficient microglia exhibit a premature aging transcriptome
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“…in the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson ’ s disease and in tauopathies such as frontotemporal dementia, but promotes amyloid clearance in models of amyloid β deposition (Cardona et al, 2006; Bhaskar et al, 2010; Lee et al, 2010; Liu et al, 2010).”
Prakash, P., Manchanda, P., Paouri, E., Bisht, K., Sharma, K., Rajpoot, J., Wendt, V., Hossain, A., Wijewardhane, P. R., Randolph, C. E., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.04.029 · Cited by 104
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Self-citationMulticolor time-stamp reveals the dynamics and toxicity of amyloid deposition
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Role of Chemokines in the Development and Progression of Alzheimer’s Disease
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From development to dysfunction: Microglia and the complement cascade in CNS homeostasis
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Fate of microglia during HIV‐1 infection: From activation to senescence?
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“In the context of neurodegenerative diseases, microglial cells play essential roles in the clearance of beta amyloid (Ab) proteins (Liu et al., 2010), the accumulation of which correlates significantly with neurocognitive impairments.”
BackgroundMoutinho, M., Puntambekar, S. S., Tsai, A. P., Coronel, I., Lin, P. B., Casali, B. T., Martinez, P., Oblak, A. L., Lasagna-Reeves, C. A., Lamb, B. T., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abl7634 · Cited by 92
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“On one hand, the lack of CX3CR1 lead to beneficial effects in models of amyloidosis by causing a reduction in amyloid-b (Ab) deposition (Lee et al., 2010, 2014; Liu et al., 2010) and in a triple transgenicmouse harboring both tau and Ab mutations by preventing neuron loss (Fuhrmann et al., 2010).”
BackgroundThe Evolving Biology of Microglia in Alzheimer's Disease
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“These findings were confirmed in additional AD mouse models [96, 97].”
ResultTwo-Photon Microscopy for Chemical Neuroscience
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IVIg protects the 3xTg-AD mouse model of Alzheimer’s disease from memory deficit and Aβ pathology
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“The impact of CX3CR1 on neurodegeneration is still debated, but previously published data demonstrate a reduction of amyloid deposits and neuronal loss, and increased in vitro phagocytosis in knockout animals for CX3CR1 [35-37].”
Background
Metadata
- Authors
- Liu, Z., Condello, C., Schain, A., Harb, R., & Grutzendler, J.
- Affiliations
- Northwestern University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-12-15
- Volume
- 30
- Issue
- 50
- Pages
- 17091-17101
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3077120
- OpenAlex
- W2086776463
- Semantic Scholar
- e9b1ff87ae8cbe2519ba93d6e6f16a75ae448b0a
- Cited by
- 275
- References
- 42
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 12 · 2023: 19 · 2022: 13 · 2021: 23 · 2020: 12 · 2019: 24 · 2018: 27 · 2017: 11 · 2016: 18 · 2015: 25 · 2014: 24 · 2013: 19 · 2012: 15
- FWCI
- 8.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ellison Medical Foundation
- National Institutes of Health
- National Institute on Aging (R01AG027855)
- 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 › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- CX3CR1, microglia, amyloid-beta, Alzheimer's disease, phagocytosis, amyloid plaques, microglial activation, microglial proliferation, phagolysosomes, chemokine receptor signaling
- MeSH terms
- CX3C Chemokine Receptor 1, Animals, Brain, Neurons, Peptide Fragments, Phagocytosis, Synapses, Amyloid beta-Peptides, Microglia, Mice, Knockout, Receptors, Chemokine, Cell Proliferation, Mice, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-20, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-20 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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