The DOI matches its Crossref record; 80 of the 80 references it cites were found in a registry or an index; 21 of the 28 sources its claims cite were checked for support.
Changes in the Synaptic Proteome in Tauopathy and Rescue of Tau-Induced Synapse Loss by C1q Antibodies
Open accessAbstract
Synapse loss and Tau pathology are hallmarks of Alzheimer's disease (AD) and other tauopathies, but how Tau pathology causes synapse loss is unclear. We used unbiased proteomic analysis of postsynaptic densities (PSDs) in Tau-P301S transgenic mice to identify Tau-dependent alterations in synapses prior to overt neurodegeneration. Multiple proteins and pathways were altered in Tau-P301S PSDs, including depletion of a set of GTPase-regulatory proteins that leads to actin cytoskeletal defects and loss of dendritic spines. Furthermore, we found striking accumulation of complement C1q in the PSDs of Tau-P301S mice and AD patients. At synapses, C1q decorated perisynaptic membranes, accumulated in correlation with phospho-Tau, and was associated with augmented microglial engulfment of synapses and decline of synapse density. A C1q-blocking antibody inhibited microglial synapse removal in cultured neurons and in Tau-P301S mice, rescuing synapse density. Thus, inhibiting complement-mediated synapse removal by microglia could be a potential therapeutic target for Tau-associated neurodegeneration.
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Written from the paper’s full text.
TL;DR
Unbiased postsynaptic density (PSD) proteomics in Tau-P301S mice identified Tau-dependent synaptic changes, including depletion of GTPase regulators and accumulation of complement C1q at synapses. C1q-blocking antibodies reduced microglial synapse engulfment and rescued synapse density in vitro and in Tau-P301S mice.
Key findings
- Label-free quantitative mass spectrometry of hippocampal PSDs from 9-month-old Tau-P301S mice identified 1,257 unique proteins, with 76 significantly decreased and 45 significantly increased relative to non-transgenic controls; core PSD scaffolds PSD-95, Homer1, and Shank3 were unchanged.
- PSDs from Tau-P301S mice were depleted of GTPase-regulatory proteins (Iqgap1, Iqgap2, Iqsec2, Kalirin, Trio); siRNA knockdown of these proteins in cultured hippocampal neurons reduced spine density by 30%–50%, and postsynaptic F-actin colocalized with Homer1 was reduced ∼30% in Tau-P301S versus nonTg CA1.
- C1q accumulated in Tau-P301S PSDs (∼9-fold above nonTg, versus 2- to 3-fold in PS2/APP PSDs), and C1q-labeled synapses were higher in Tau-P301S CA1 (18.2% ± 0.9%) than nonTg (8% ± 1.6%) at 9 months; C1q levels correlated with AT8 phospho-Tau.
- Microglial engulfment of synaptic puncta increased ∼2-fold in Tau-P301S CA1 at 9 months, and a C1q-blocking antibody reduced PSD-95 or Synapsin puncta within microglial lysosomes by ∼50% and slightly but significantly increased synapse density 5 days after hippocampal injection.
Methods
- Tau-P301S transgenic mice, PS2/APP mice, and non-transgenic littermates were used; all mice were female, and PSD analyses focused on 9 months of age, before overt hippocampal neurodegeneration. Human postmortem superior frontal gyrus tissue from early-stage AD, autopsy-confirmed AD, and age-matched controls was also analyzed.
- PSD fractions were isolated and analyzed by label-free quantitative mass spectrometry (n = 3 Tau-P301S, n = 3 nonTg), with validation by western blotting, immunoprecipitation, STED super-resolution microscopy, correlative light-electron microscopy, immunoEM, FACS-sorted microglia, electrophysiology, behavior, MRI, and stereotaxic anti-C1q antibody injection.
- Differential protein abundance was defined as log2 fold-change > 0.5 and adjusted p < 0.05; Gene Ontology enrichment used hypergeometric tests with p < 0.01 and at least 4 overlapping genes. Data are shown as mean ± SEM.
Limitations
- Stated: biochemical PSD analysis provides an “average” synapse view and may hide heterogeneity among individual PSDs.
- Stated: a single anti-C1q injection did not improve LTP at 5 days; other tauopathy-induced PSD changes may persist, and longer treatment may be needed for functional benefit.
- Stated: C1q also deposits at non-synaptic sites, and tauopathy may not be absolutely necessary for synaptic C1q buildup because amyloidosis can stimulate it and early AD tissue can show C1q before AT8-immunoreactive phospho-Tau. Evident: the MS proteomics used only n = 3 per genotype, human PSD data came from a small number of SFG tissues, and the in vivo rescue was assessed only 5 days after a single injection.
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Claims the paper makes
108 Own result · 37 Own interpretation · 15 Own method · 11 Partly supported · 3 No basis given · 1 Supported · 1 No full text of the sources · 1 Not checked yet · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“recent evidence in various neurodegenerative models points to an important role for synapse loss via microglial phagocytosis (Hong et al., 2016a; Lui et al., 2016; Vasek et al., 2016”
What the sources say
- Not matchedcites Hong et al., 2016a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites Lui et al., 2016 source
The Results section, “Complement Protein C1qa Promotes Synaptic Pruning by Grn−/− Microglia” (page not available), reports fewer synapses near progranulin-deficient microglia and more synapses inside their lysosomes. The Discussion identifies selective synapse loss in these mice as a neurodegenerative feature. This paper supports the claim for one of the models covered by the sentence’s multiple citations. (LLM, conf=0.92)
- Partly supportedcites Vasek et al., 2016 sourceExperimental — accuracy not yet measured
The paper’s synapse-loss passage (section labelled Abstract; page unavailable) reports presynaptic terminals inside microglial lysosomes in West Nile virus-infected mice, supporting a role for microglial phagocytosis. This source studies virus-induced memory impairment, not various neurodegenerative models; that scope is not supported by this citation alone. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Not matched
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
“Notably, there was a significant enrichment of such disease-associated proteins among the decreased proteins in Tau-P301S PSDs (Figure 2E; p = 0.0008)”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“Cntn1, Rimbp2, and Ctnna2, whose biology is not well understood, were significantly decreased in Tau-P301S PSDs”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“Pathological Tau accumulation alters protein composition of PSD in Tau-P301S mice”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“was associated with augmented microglial engulfment of synapses”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“The total hippocampal levels of Prrt1, SynGAP1, and Ezrin were unchanged”
plain- Asserted: passes — The authors put it forward as true.
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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 identified 24 proteins from familial AD or AD genome-wide association studies (GWASs) in the PSD proteome.”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“AT8 staining was virtually undetectable in non-transgenic (nonTg) brains at all ages.”
plain- Asserted: passes — The authors put it forward as true.
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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
“As expected, overall phospho-Tau levels were highly elevated in Tau-P301S mice compared with nonTg mice.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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
“A C1q-blocking antibody inhibited microglial synapse removal in cultured neurons and in Tau-P301S mice, rescuing synapse density”
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.
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- It may state two separate claims as one. 55
- Probably not a substantial claim. 24
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“infiltration of pathological Tau can disrupt synaptic functions and lead to synapse loss (Hoover et al., 2010; Zhao et al., 2016”
What the sources say
- Partly supportedcites Hoover et al., 2010 sourceExperimental — accuracy not yet measured
The Discussion reports that pathological tau mislocalization into dendritic spines suppresses synaptic function. It places this impairment before synapse loss and describes later spine loss as a hypothesis, rather than demonstrating that tau infiltration leads to synapse loss. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites Zhao et al., 2016 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“where variants in the underlying genes are associated with epilepsy, autism, schizophrenia, or intellectual disability (De Rubeis et al., 2014; Russell et al., 2014; Sadybekov et al., 2017; Shoubridge et al., 2010; Yang et al., 2014”
What the sources say
- Partly supportedcites De Rubeis et al., 2014 sourceExperimental — accuracy not yet measured
The Transmission and De novo Association section identifies TRIO among genes previously found mutated in people with autism, and Extended Data Table 1 lists an IQGAP2 deletion in an ASD subject. The passages do not establish the claimed associations for IQGAP1, IQSEC2, or Kalirin, or link the named genes individually to epilepsy, schizophrenia, or intellectual disability. Page numbers are not available in our copy. (LLM, conf=0.86)
- Supportedcites Russell et al., 2014 source
The Introduction states that KALRN has been associated with schizophrenia risk through resequencing and association analyses. This supports the Kalirin–schizophrenia part of the multi-citation claim; the paper does not establish that its own rare variant increases schizophrenia risk. (LLM, conf=0.88)
- Supportedcites Sadybekov et al., 2017 source
The Results section (‘ASD-related mutations in Trio’) reports de novo TRIO variants in individuals with ASD or related disorders, including intellectual disability. In this multi-citation sentence, the paper supports the association for TRIO; the other genes are not attributed specifically to this source. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“it is Tau pathology and synapse loss that temporally correlate with cognitive impairment and precede overt neurodegeneration (Jack et al., 2010; Scheff et al., 2006; Spires-Jones and Hyman, 2014”
What the sources say
- Partly supportedcites Jack et al., 2010 sourceExperimental — accuracy not yet measured
The 'AD clinical features and pathological changes' section links NFTs and especially synapse loss to clinical symptoms and cognitive impairment. The 'Neurodegenerative biomarkers are temporally ordered' section says CSF tau and FDG-PET abnormalities precede MRI-detected atrophy, not neurodegeneration generally; it describes synapse loss itself as a form of neurodegeneration. The claim therefore overstates what precedes what. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites Scheff et al., 2006 source
- Partly supportedcites Spires-Jones and Hyman, 2014 sourceExperimental — accuracy not yet measured
The paper states that tau tangles correlate with cognitive decline (Abstract; “Alzheimer’s disease pathology – tau”) and that synapse loss is the strongest pathological correlate of dementia (“Synaptic dysfunction, synapse loss and relationships to pathology”; page unavailable). It does not establish that both tau pathology and synapse loss precede overt neurodegeneration; the Abstract instead describes synapse degeneration as part of the neurodegenerative process. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In particular, C1q, the initiator of the classical complement pathway, which is produced by microglia in the brain, colocalizes with synaptic markers and may contribute to synapse loss in several neurodegenerative models (Hong et al., 2016a; Lui et al., 2016; Vasek et al., 2016”
What the sources say
- Not matchedcites Hong et al., 2016a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Supportedcites Lui et al., 2016 source
The Results section on age-dependent complement activation reports C1qa next to synaptophysin-positive synapses in Grn−/− mice. The Results section on synaptic pruning says C1qa is made by microglia and that its loss reduces microglial pruning. This paper supports the Grn−/− model as one example within the several-model statement, which cites multiple papers. (LLM, conf=0.88)
- Partly supportedcites Vasek et al., 2016 sourceExperimental — accuracy not yet measured
The paper’s Abstract identifies C1QA as an initiator of the classical complement cascade, detects its expression alongside the microglial marker IBA1, and reports increased colocalization with VGlut1-positive presynaptic terminals. It links complement and microglia to synapse loss in West Nile virus-infected mice, but does not establish that C1q contributes to synapse loss in several neurodegenerative models. (LLM, conf=0.87)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Not matched
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In the paper
“During progression of AD and other tauopathies, abnormally phosphorylated forms of Tau aggregate and accumulate in the somatodendritic compartment in neurons and can localize to synapses (Ittner and Götz, 2011; Tai et al., 2012”
What the sources say
- Not checked — no full text of the sourcecites Ittner and Götz, 2011 source
- Partly supportedcites Tai et al., 2012 sourceExperimental — accuracy not yet measured
The sections “p-tau is Localized to Both Presynaptic and Postsynaptic Sites” and “Synaptic tau in the Context of Other AD Lesions” (pages unavailable) report that hyperphosphorylated tau oligomers accumulate at AD synapses, including postsynaptic sites. The cited paper does not establish the broader claim of somatodendritic accumulation in neurons across AD and other tauopathies. (LLM, conf=0.86)
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.
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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
“Synapse loss is a hallmark of Alzheimer’s disease (AD) and other tauopathies and is central to the neurodegenerative process (Spires-Jones and Hyman, 2014”
What the sources say
- Partly supportedcites Spires-Jones and Hyman, 2014 sourceExperimental — accuracy not yet measured
The Abstract describes synaptic changes as central to the AD disease process, and “Synaptic dysfunction, synapse loss and relationships to pathology” calls synapse loss the strongest pathological correlate of dementia in AD. That section also reports fewer synapses on tangle-bearing neurons in mouse models of tauopathy, but does not establish synapse loss as a hallmark of other human tauopathies. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The postsynaptic density (PSD) of excitatory synapses is usually located on dendritic spines, whose growth and stability depend on the actin cytoskeleton and whose dynamic modulation is essential for synaptic integrity and plasticity (Fukazawa et al., 2003; Okamoto et al., 2004”
What the sources say
- Partly supportedcites Fukazawa et al., 2003 sourceExperimental — accuracy not yet measured
The Introduction describes dynamic actin in dendritic spines, and the Abstract and Discussion link spine actin reorganization to spine morphology and maintenance of hippocampal LTP. Our copy does not establish that the PSD of excitatory synapses is usually on spines, or that spine growth, stability, and synaptic integrity generally depend on actin. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites Okamoto et al., 2004 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. It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“During development, complement-dependent synaptic pruning by microglia is modulated by synaptic activity such that active synapses are preserved and less active synapses are removed (Schafer et al., 2012”
What the sources say
- Supportedcites Schafer et al., 2012 source
The Results section, “Microglia-mediated engulfment of RGC inputs is regulated by neural activity,” reports preferential engulfment of inputs from the less active eye rather than the more active eye. The Discussion identifies CR3/C3-dependent signaling as a mechanism of microglial pruning and proposes that activity and complement work cooperatively. Preservation here is relative, not a claim that every active synapse survives. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Iqgap1, Iqgap2, Iqsec2, Kalirin, and Trio are localized in dendritic spines of hippocampal neurons (Figure S3A) and enriched in PSD fractions of the mouse hippocampus (Figure S3B)”
What the sources say
- Partly supportedcites Gao et al., 2011 sourceExperimental — accuracy not yet measured
The Results section reports that IQGAP1 is present in hippocampal neuronal processes and that its loss reduces dendritic spine density. The Discussion identifies IQGAP1 in complexes with PSD-95, but neither passage establishes localization within spines or enrichment in mouse hippocampal PSD fractions. The paper does not establish those claims for IQGAP2, IQSEC2, Kalirin, or Trio either. Page numbers were not available in our copy. (LLM, conf=0.87)
- Partly supportedcites Myers et al., 2012 sourceExperimental — accuracy not yet measured
The Results section, “BRAG1 localization to the postsynaptic density” (page unavailable), identifies BRAG1 as IQSec2 and reports its colocalization with PSD-95 in rat hippocampal neurons. It does not establish the localization of Iqgap1, Iqgap2, Kalirin, or Trio, or enrichment of the five proteins in PSD fractions from mouse hippocampus. (LLM, conf=0.88)
- Partly supportedcites Xie et al., 2007 sourceExperimental — accuracy not yet measured
The Results say kalirin-7 is enriched in dendritic spines, and the Discussion describes it as anchored to the PSD in spines. Our copy does not establish the claimed localization or PSD-fraction enrichment for Iqgap1, Iqgap2, Iqsec2, or Trio, nor does it establish enrichment of all five proteins in mouse hippocampal PSD fractions. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Recently, using light sheet fluorescence microscopy and CLEM, microglia have been shown to “nibble” and phagocytose presynaptic, but not postsynaptic, terminals during development (Weinhard et al., 2018”
What the sources say
- Partly supportedcites Weinhard et al., 2018 sourceExperimental — accuracy not yet measured
The Discussion reports nibbling (trogocytosis) of presynaptic boutons and axons, with no evidence of postsynaptic material being eliminated. But it distinguishes this partial uptake from phagocytosis of entire synapses, so the claim overstates the finding if “phagocytose presynaptic terminals” means engulfing whole terminals. (LLM, conf=0.87)
boosteddirect- 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.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“complement activation and synapse loss seems to be a feature of multiple neurological diseases, including progranulin-deficient frontotemporal dementia (Lui et al., 2016”
What the sources say
- Supportedcites Lui et al., 2016 source
The citation is attached to progranulin-deficient frontotemporal dementia, not the other listed diseases. The Discussion section on FTLD reports complement activation in patients with GRN mutations, while the section on PGRN deficiency reports complement-dependent synapse loss in a mouse model of FTLD. (LLM, conf=0.90)
- Supportedcites Vasek et al., 2016 source
The cited paper supports the virus-induced memory impairment example in the list. Its Abstract reports complement-mediated loss of hippocampal presynaptic terminals after West Nile virus infection and impaired spatial learning in recovered mice. The other diseases listed are not attributed to this citation. (LLM, conf=0.93)
- Partly supportedcites Stevens et al., 2007 sourceExperimental — accuracy not yet measured
The Discussion reports C1q at retinal synapses early in a mouse model of glaucoma, before or alongside synapse loss, and suggests complement-mediated elimination may occur there. Our copy does not address progranulin-deficient frontotemporal dementia, virus-induced memory impairment, or CNS lupus, so it supports only the glaucoma example in the supplied claim. (LLM, conf=0.86)
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.
- 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
“C1q-blocking antibody prevents microglial synapse removal and rescues synapse density”
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 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
“A total of 1,257 unique proteins were identified in the PSD, of which 76 were significantly decreased and 45 significantly increased in Tau-P301S PSD fractions, relative to nonTg”
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.
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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
“Electrophysiological analysis of hippocampal brain slices from 9-month-old Tau-P301S mice showed exaggerated short-term synaptic facilitation (increased paired-pulse ratio; PPR), and significantly reduced long-term potentiation (LTP) of excitatory postsynaptic potentials (EPSPs) and population spikes”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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
“Notably, AT8, AT100, and AT180 antibodies (which recognize phosphoepitopes that are abundant in pathological aggregated and filamentous Tau of human AD) showed an elevated signal in Tau-P301S mice that was markedly enriched in PSD fractions and only weak or undetectable in nonTg mice”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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 12 months, Tau-P301S mice showed obvious neurodegeneration and clear hippocampal atrophy”
boosted- 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
“Tau-P301S mice behaved similarly to nonTg mice at 6 and 9 months of age but showed elevated total motor activity at 12 months of age”
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
“A C1q-blocking antibody inhibited microglial synapse removal in cultured neurons and in Tau-P301S mice, rescuing synapse density”
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 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
“When AT8 phospho-Tau antibody was used in immunoEM, the AT8 immunogold particles were often found on dense aggregates (Figures S2F and S2G), which were also detected in presynaptic termini and in dendritic spines”
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.
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
“Tau immunoblots of Tau-P301S brain, however, showed a complex banding pattern with marked differences between the PSD and total lysate, suggesting that specific Tau species were enriched in synapses”
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 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
“In the Morris water maze test, which measures spatial learning and memory, 9-month-old Tau-P301S-mice learned more slowly than nonTg controls, traveling a greater distance to the target platform and spending less time in the target quadrant”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
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
“While total Tau was increased in Tau-P301S mice, there was no significant difference in Tau levels in lysates versus PSD fractions within either nonTg or Tau-P301S mice when the total immunoreactivity of all Tau-bands was quantified”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
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
“hTau was readily detectable in presynaptic termini, often associated with synaptic vesicles, and in the majority (>80%) of postsynaptic compartments close to the PSD”
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.
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
“PSDs of tauopathy-affected neurons are depleted of a specific set of intracellular signaling proteins with known postsynaptic functions (small GTPase regulators) while accumulating an extracellular protein involved in innate immunity (complement C1q).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
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 confirmed that C1q was greatly increased (with high inter-animal variability) in PSDs of 9-month-old Tau-P301S hippocampi and barely detectable in the nonTg PSD (Figure 4A).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
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
“C1q was elevated in total lysate and highly enriched in the PSD fractions from EAD as well as AD patients (Figure 5D).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
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
“In nonTg mice, hippocampal C1q immunostaining stayed roughly constant from 6–12 months of age, whereas in Tau-P301S mice it increased in intensity at 9 and 12 months (Figure S4B).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
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
“Despite amelioration of synapse density, a single injection of anti-C1q did not improve LTP.”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
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
“The average level of C1q in the PSD of Tau-P301S mice was elevated ∼9-fold above nonTg controls, whereas it was increased only 2- to 3-fold in the PSD of PS2/APP mice (Figure 4G).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“AT8 immunoreactivity was enriched in PSD fractions compared to total lysates from AD brains, similar to Tau-P301S mice.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
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
“Control IgG showed diffuse staining in hippocampus and cortex (ipsilateral > contralateral) with no specific colocalization with C1q (Figures 8A and 8B).”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
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 also found elevated C1q in AD patient brains, not only in bulk tissue, but also in purified PSD fractions, consistent with synaptic tagging by C1q in AD.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“Phallacidin had no effect on spines in control cultures but restored spine density in neurons treated with siRNAs targeting Iqsec2, Kalirin, Trio, or Iqgap1 and Iqgap2, or even led to spine density greater than control neurons (Figure 3C).”
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Although conspicuously localized at synapses in tauopathy mice, C1q is also deposited at non-synaptic sites on neurons and possibly other cells”
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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
“The injected anti-C1q antibodies were present throughout the ipsilateral hippocampus and, to a lesser extent, the contralateral side (Figures 8A and 8B).”
plain- Asserted: passes — The authors put it forward as true.
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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
“antibodies against PSD-95 (but not Gephyrin, the scaffold of GABAergic synapses) co-immunoprecipitated C1q and hTau from hippocampal lysates, confirming that C1q and Tau are specifically in the PSD-95 complex associated with excitatory synapses (Figure 4F).”
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“synapse density, as measured by PSD-95 clusters, was reduced by ∼30% on “microglia-proximal” dendrites (overlapping or in contact with Iba1+ cells) but was unchanged on “microglia-distant” dendrites (>30 μm separated from Iba1+ cells) (Figure S7C)”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
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
“The amount of C1q co-immunoprecipitated with PSD-95 was greater from Tau-P301S than from nonTg hippocampus and mirrored the amount of co-immunoprecipitated phospho-Tau”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“the increase in synaptic C1q labeling in Tau-P301S mice was mainly driven by augmented postsynaptic C1q, as the percentage of presynaptic labeling by C1q was only slightly increased between Tau-P301S and nonTg mice (Figure 4D).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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
“The density of Gephyrin clusters was not affected by microglia or by addition of C1q antibodies”
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“In brains injected with anti-C1q, the intensity of C1q staining was reduced in the ipsilateral hippocampus, while control IgG injection had no effect (Figures 8A and 8B).”
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 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
“mean levels of C1q in superior frontal gyrus (SFG) lysates were increased ∼1.5-fold in patients with a diagnosis of early-stage AD (EAD) and ∼2-fold elevated in patients with autopsy-confirmed AD (Figure 5A; Table S3).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
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 also analyzed the downstream complement factor C3, which was unchanged in SFG lysates of EAD patients but increased ∼2-fold in AD patients (Figure 5A)”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“C1q tags Tau-affected synapses, leading to microglial engulfment and synapse loss”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Normally, Tau is enriched in axons, where it interacts with microtubules (MTs) and may regulate MT polymerization and dynamics, axonal outgrowth, and transport (Wang and Mandelkow, 2016”
What the sources say
- Not checked — no full text of the sourcecites Wang and Mandelkow, 2016 source
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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that these proteins are specifically depleted from (Prrt1, SynGAP1) or augmented (Ezrin), in the PSD”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
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 biochemical and imaging data show that there is increased microglial engulfment of synapses (both pre- and postsynaptic compartments) in Tau-P301S mice at 9 months of age, temporally correlating with accumulation of C1q and a drop in synapse density.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“which can lead to dysregulation of the actin cytoskeleton and potentially contribute to the spine loss seen in AD and other tauopathies.”
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.
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
“Sample size was chosen according to that used for similar experiments in previously published literature.”
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no 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
“our results demonstrate that C1q antibodies can reduce synapse removal by microglia and lead to a recovery of synapse density in cultures and in vivo.”
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
“All behavioral scorings, electrophysiological, microscopic and histological analyses were carried out by experimenters blind to genotype and treatment groups.”
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.
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 further filtered to a confidence score of 83 or greater.”
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.
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
“This rescue of synapse number suggests an ongoing dynamic turnover of synapses in the Tau-P301S brain that can be rebalanced in a favorable direction by neutralization of C1q.”
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
“consistent with the idea that Tau pathology causes C1q accumulation and that C1q associates with synapses that have been affected by phospho-Tau.”
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.
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
“Animals were always processed in pairs (1 nonTg and 1 Tau-Tg) and sorted simultaneously in two BD FACS ARIA sorters.”
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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting that other structures could be targets of microglial engulfment or complement-mediated damage.”
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
“while tauopathy seems to be sufficient to induce the C1q tagging of synapses, it may not be absolutely necessary for this outcome, as synaptic C1q buildup is also stimulated by amyloidosis and can occur in early AD brain tissue prior to the detection of AT8-immunoreactive phospho-Tau (see Figure 5D).”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The biochemical analysis of the PSD provides only a view of the “average” synapse and so may hide the heterogeneity of changes in individual PSDs that occur in response to tauopathy.”
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
“Peak areas were normalized on a sample-by-sample basis to ensure equal median peak intensities across all samples.”
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.
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
“Filtered peptides were subsequently filtered to a 2% protein FDR.”
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
“All animal studies were authorized and approved by the Genentech Institutional Animal Care and Use Committee.”
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.
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
“further suggesting that microglia selectively remove excitatory synapses without damaging the dendrite (Figures 7A and 7B).”
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
“suggesting that microglia engulf synapses and perhaps not neuronal soma and arguing against a non-specific contamination of the microglial prep by neuronal cells.”
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.
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, segmentation overlays, and data were reviewed by a pathologist.”
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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data indicate that C1q is enriched in human AD brains and appears to be associated with synapses in EAD and AD.”
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.
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
“Peptide-spectral matches were first filtered to a false discovery rate (FDR) of 5% at the peptide level using a linear discriminant approach.”
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
“Human samples were procured with Ethics Committee approval and written informed consent.”
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
“Further stringent filters were applied to the results, requiring p-values < 0.01, and at least 4 differentially abundant genes overlapping a given ontology category.”
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
“No outlier analysis was performed or data points excluded.”
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
“The experimenter was blinded to the treatment of analyzed neurons.”
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
“Experimenters were blinded whenever possible to experimental condition during data acquisition or quantification.”
hedged- 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
“In all experiments, animals were randomly assigned to experimental or treatment groups and matched for age and littermate controls.”
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.
The paper relies on this without support.
An unbiased examination of the effects of Tau pathology on the protein composition of synapses has not been performed.
“An unbiased examination of the effects of Tau pathology on the protein composition of synapses has not been performed.”
The paper relies on this without support.
C1q is a secreted protein produced mainly by microglia.
“Given that C1q is a secreted protein produced mainly by microglia”
The paper relies on this without support.
Microglia are a major source of C1q production in the brain.
“given that microglia are a major source of C1q production in the brain”
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 cited source doesn’t support the claim as written.
In the citing paper
“Soluble factors secreted by activated microglia under conditions of chronic inflammation have been thought to mediate aberrant synaptic phagocytosis inducing synapse loss and cognitive impairment (Butler et al., 2021; Dejanovic et al., 2018).”
From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Dejanovic et al., 2018
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Thus the increased activity of the complement system may accelerate the development of AD symptoms.”
From Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression (2020) · cites this paper as Dejanovic et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“microglial-expressed complement components, including C1q, are thought to bind to synapses and enable phagocytosis by microglia [75, 103]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [75]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“in normal aging [300] and in tauopathy patients [75], C1q is dramatically upregulated and is shown to co-localize with hyperphosphorylated tau, plaques and neurofibrillary tangles in AD brain sections [1, 219, 282]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [75]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Microglia can phagocytose tau-laden synapses or entire neurons [36, 75], promoting neurodegeneration and memory loss.”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [75]
Experimental — accuracy not yet measured
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
“However, these studies relied on immunohistochemical staining of synaptic markers, which does not yield image resolution that is comparable to the methods employed here.”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Dejanovic et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The C3a receptor is expressed by microglia and C1q-mediated injury is blocked by antibodies to C1q, suggesting neuroinflammation-mediated injury likely involves a multicellular response, an important component of which is elevated microglial-mediated synaptic phagocytosis (Dejanovic et al., 2018).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Dejanovic et al., 2018
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“for example, SORLA upregulation can suppress induction of key drivers of tau pathogenesis such as C1q (Dejanovic, Huntley et al. 2018, Dejanovic, Wu et al. 2022) and Apoe (Shi, Manis et al. 2019).”
From SORLA up-regulation suppresses pathological effects in aged tauopathy mouse brain (2026) · cites this paper as Dejanovic, Huntley et al. 2018
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“complement activation, which is important for microglial phagocytosis, can exacerbate synaptic loss [152, 284, 291] and contribute to memory loss and cognitive decline [75]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [75]
The cited source says what the claim attributes to it.
In the citing paper
“Tau, including phosphorylated tau, is present in presynaptic and postsynaptic compartments in the PS19 mouse model (Yoshiyama et al., 2007, Dejanovic et al., 2018, McInnes et al., 2018).”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Dejanovic et al., 2018
The cited source says what the claim attributes to it.
In the citing paper
“Such phagocytosis can be stimulated by opsonins at damaged synapses, such as C1q (Dejanovic et al., 2018; Gratuze et al., 2020; Hong et al., 2016; Stevens et al., 2007).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Dejanovic et al., 2018
The cited source says what the claim attributes to it.
In the citing paper
“The C3a receptor is expressed by microglia and C1q-mediated injury is blocked by antibodies to C1q, suggesting neuroinflammation-mediated injury likely involves a multicellular response, an important component of which is elevated microglial-mediated synaptic phagocytosis (Dejanovic et al., 2018).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Dejanovic et al., 2018
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“The C3a receptor is expressed by microglia and C1q-mediated injury is blocked by antibodies to C1q, suggesting neuroinflammation-mediated injury likely involves a multicellular response, an important component of which is elevated microglial-mediated synaptic phagocytosis (Dejanovic et al., 2018).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Dejanovic et al., 2018
Experimental — accuracy not yet measuredIn the citing paper
“Furthermore, microglia could also phagocytize synapses that contain aggregated tau via synaptic tagging of C1q, leading to a decline in synapse density.390”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [390]
In the citing paper
“A C1q-blocking antibody could inhibit microglial synapse removal and rescue synapse density in cultured neurons and Tau-P301S mice.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [390]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Self-check results appear here once an independent check has confirmed them.
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
“Bialas, 2017, Microglia-dependent synapse loss in type I interferon-mediated lupus, Nature, 546, 539, 10.1038/nature22821”
Cited work 10.1038/nature22821 · retracted 2020-02-05 · notice 10.1038/s41586-020-1949-x · this paper published 2018-12
Citations
Cites
1 retracted
Microglia-dependent synapse loss in type I interferon-mediated lupus
Bialas, A. R., Presumey, J., Das, A., van der Poel, C. E., Lapchak, P. H., Mesin, L., Victora, G., Tsokos, G. C., Mawrin, C., Herbst, R., et al. (2017) · Nature · doi:10.1038/nature22821 · Cited by 197
RetractedHypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade
Jack, C. R., Knopman, D. S., Jagust, W. J., Shaw, L. M., Aisen, P. S., Weiner, M. W., Petersen, R. C., & Trojanowski, J. Q. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70299-6 · Cited by 4,806
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089
Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326
The Classical Complement Cascade Mediates CNS Synapse Elimination
Stevens, B., Allen, N. J., Vazquez, L. E., Howell, G. R., Christopherson, K. S., Nouri, N., Micheva, K. D., Mehalow, A. K., Huberman, A. D., Stafford, B., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.036 · Cited by 3,313
Synaptic, transcriptional and chromatin genes disrupted in autism
Study, T. D., De Rubeis, S., Autism, H. M. C. F., UK10K Consortium, The Autism Sequencing Consortium, He, X., Goldberg, A. P., Poultney, C. S., Samocha, K., Ercument Cicek, A., et al. (2014) · Nature · doi:10.1038/nature13772 · Cited by 2,746
Schizophrenia risk from complex variation of complement component 4
Sekar, A., Bialas, A. R., de Rivera, H., Davis, A., Hammond, T. R., Kamitaki, N., Tooley, K., Presumey, J., Baum, M., Van Doren, V., et al. (2016) · Nature · doi:10.1038/nature16549 · Cited by 2,394
Tau in physiology and pathology
Wang, Y., & Mandelkow, E. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.1 · Cited by 2,251
Cited by
Sorted by citations
Items 101–200 of 503
van Olst, L., Verhaege, D., Franssen, M., Kamermans, A., Roucourt, B., Carmans, S., Ytebrouck, E., van der Pol, S. M. A., Wever, D. D., Popovic, M. A., et al. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.01.003 · Cited by 76
Aryal, S., Bonanno, K., Song, B. J., Mani, D. R., Keshishian, H., Carr, S. A., Sheng, M., & Dejanovic, B. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112497 · Cited by 77
Self-citationTang, S. J., Fesharaki‐Zadeh, A., Takahashi, H., Nies, S. H., Smith, L. M., Luo, A., Chyung, A. S., Chiasseu, M., & Strittmatter, S. M. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00976-9 · Cited by 74
Synaptic pruning of murine adult-born neurons by microglia depends on phosphatidylserine
Kurematsu, C., Sawada, M., Ohmuraya, M., Tanaka, M., Kuboyama, K., Ogino, T., Matsumoto, M., Oishi, H., Inada, H., Ishido, Y., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20202304 · Cited by 69
Role of glia and extracellular matrix in controlling neuroplasticity in the central nervous system
Dzyubenko, E., & Hermann, D. M. (2023) · Seminars in Immunopathology · doi:10.1007/s00281-023-00989-1 · Cited by 73
The Importance of Complement-Mediated Immune Signaling in Alzheimer’s Disease Pathogenesis
Batista, A. F., Khan, K., Papavergi, M.-T., & Lemere, C. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25020817 · Cited by 72
Sharma, S., Chitranshi, N., Wall, R. V., Basavarajappa, D. K., Gupta, V., Mirzaei, M., Graham, S. L., Klistorner, A. I., & You, Y. (2021) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2021.06.001 · Cited by 66
Meng, J., Han, L., Zheng, N., Wang, T., Xu, H., Jiang, Y., Wang, Z., Liu, Z., Zheng, Q., Zhang, X., et al. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.1644-21.2022 · Cited by 66
Györffy, B. A., Tóth, V., Török, G., Gulyássy, P., Kovács, R. Á., Vadászi, H., Micsonai, A., Tóth, M. E., Sántha, M., Homolya, L., et al. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03468-0 · Cited by 65
Lv, Z., Chen, L., Chen, P., Peng, H., Rong, Y., Hong, W., Zhou, Q., Li, N., Li, B., Paolicelli, R. C., et al. (2024) · Neuron · doi:10.1016/j.neuron.2023.12.003 · Cited by 65
Complement-mediated synapse loss in Alzheimer’s disease: mechanisms and involvement of risk factors
Wen, L., Bi, D., & Shen, Y. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.11.010 · Cited by 64
Hu, Y., & Tao, W. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.01.006 · Cited by 64
The Role of Glial Cells in Synaptic Dysfunction: Insights into Alzheimer's Disease Mechanisms
Yu, Y., Chen, R., Mao, K., Deng, M., & Li, Z. (2023) · Aging and Disease · doi:10.14336/ad.2023.0718 · Cited by 62
Correcting abnormalities in miR‐124/PTPN1 signaling rescues tau pathology in Alzheimer’s disease
Hou, T., Zhou, Y., Zhu, L., Wang, X., Pang, P., Wang, D., Liuyang, Z., Man, H., Lu, Y., Zhu, L., et al. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.14961 · Cited by 60
Ma, S.-X., Seo, B. A., Kim, D., Xiong, Y., Kwon, S., Brahmachari, S., Kim, S., Kam, T., Nirujogi, R. S., Kwon, S. H., et al. (2021) · Journal of Proteome Research · doi:10.1021/acs.jproteome.0c01002 · Cited by 59
The complement system in neurodegenerative diseases
Nimmo, J., Byrne, R. A. J., Daskoulidou, N., Watkins, L. M., Carpanini, S. M., Zelek, W. M., & Morgan, B. P. (2024) · Clinical Science · doi:10.1042/cs20230513 · Cited by 60
Panitch, R., Hu, J., Chung, J., Zhu, C., Meng, G., Xia, W., Bennett, D. A., Lunetta, K. L., Ikezu, T., Au, R., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01266-z · Cited by 59
Adrian, M., Weber, M., Tsai, M., Glock, C., Kahn, O. I., Phu, L., Cheung, T. K., Meilandt, W. J., Rose, C. M., & Hoogenraad, C. C. (2023) · Nature Communications · doi:10.1038/s41467-023-41891-6 · Cited by 58
Self-citationResveratrol Rescues Tau-Induced Cognitive Deficits and Neuropathology in a Mouse Model of Tauopathy
Sun, X., Dong, Q.-X., Zhu, J., Sun, X., Zhang, L., Qiu, M., Yu, X., & Liu, R. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190801153751 · Cited by 58
The Cell Biology of Tau Secretion
Merezhko, M., Uronen, R., & Huttunen, H. J. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.569818 · Cited by 65
Complement cascade functions during brain development and neurodegeneration
Fatoba, O., Itokazu, T., & Yamashita, T. (2021) · FEBS Journal · doi:10.1111/febs.15772 · Cited by 59
Kalirin and Trio: RhoGEFs in Synaptic Transmission, Plasticity, and Complex Brain Disorders
Paskus, J. D., Herring, B. E., & Roche, K. W. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.05.002 · Cited by 56
Platelet biomarkers for a descending cognitive function: A proteomic approach
Yu, H., Liu, Y., He, B., He, T., Chen, C., He, J., Yang, X., & Wang, J. (2021) · Aging Cell · doi:10.1111/acel.13358 · Cited by 56
Novel Antibodies for the Simple and Efficient Enrichment of Native O-GlcNAc Modified Peptides
Burt, R. A., Dejanovic, B., Peckham, H. J., Lee, K. A., Li, X., Ounadjela, J. R., Rao, A., Malaker, S. A., Carr, S. A., & Myers, S. A. (2021) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2021.100167 · Cited by 55
Self-citationUnderstanding microglial diversity and implications for neuronal function in health and disease
Schepper, S. D., Crowley, G., & Hong, S. Y. (2020) · Developmental Neurobiology · doi:10.1002/dneu.22777 · Cited by 54
Astrocyte-dependent circuit remodeling by synapse phagocytosis
Park, J., & Chung, W. (2023) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2023.102732 · Cited by 56
Huang, P., Zhou, Q., Lin, Q., Lin, L., Wang, H., Chen, X., Jiang, S., Fu, H. Q., & Deng, Y. (2019) · Brain Pathology · doi:10.1111/bpa.12798 · Cited by 55
Bourel, J., Planche, V., Dubourdieu, N., Oliveira, A., Séré, A., Ducourneau, E.-G., Tible, M., Maitre, M., Lesté-Lasserre, T., Nadjar, A., et al. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105533 · Cited by 58
Potential neurobiological links between social isolation and Alzheimer's disease risk
Drinkwater, E., Davies, C., & Spires‐Jones, T. L. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15373 · Cited by 56
The role of glia in protein aggregation
Li, Q., & Haney, M. S. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105015 · Cited by 54
Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state
de Gérando, A. M., d’Orange, M., Augustin, E., Joséphine, C., Aurégan, G., Gaudin, M., Guillermier, M., Hérard, A., Stimmer, L., Petit, F., et al. (2021) · Brain · doi:10.1093/brain/awab011 · Cited by 50
Effect of APOE alleles on the glial transcriptome in normal aging and Alzheimer’s disease
Serrano-Pozo, A., Li, Z., Noori, A., Nguyen, H. N., Mezlini, A., Li, L., Hudry, E., Jackson, R. J., Hyman, B. T., & Das, S. (2021) · Nature Aging · doi:10.1038/s43587-021-00123-6 · Cited by 49
Microglia: Lifelong modulator of neural circuits
Ikegami, A., Haruwaka, K., & Wake, H. (2019) · Neuropathology · doi:10.1111/neup.12560 · Cited by 49
The role of the complement system in Multiple Sclerosis: A review
Saez-Calveras, N., & Stüve, O. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.970486 · Cited by 51
Molecular mechanisms of schizophrenia: Insights from human genetics
Farsi, Z., & Sheng, M. (2023) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2023.102731 · Cited by 49
Self-citationCSMD1 regulates brain complement activity and circuit development
Baum, M. L., Wilton, D. K., Fox, R. G., Carey, A. E., Hsu, Y.-H. H., Hu, R., Jäntti, H., Fahey, J. B., Muthukumar, A. K., Salla, N., et al. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.03.041 · Cited by 50
Ocular Dominance Plasticity in Binocular Primary Visual Cortex Does Not Require C1q
Welsh, C. A., Stephany, C.-É., Sapp, R. W., & Stevens, B. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.1011-19.2019 · Cited by 51
A novel pathway regulates social hierarchy via lncRNA AtLAS and postsynaptic synapsin IIb
Ma, M., Xiong, W., Hu, F., Deng, M., Huang, X., Chen, J., Man, H., Lu, Y., Liu, D., & Zhu, L. (2020) · Cell Research · doi:10.1038/s41422-020-0273-1 · Cited by 49
P2X7-deficiency improves plasticity and cognitive abilities in a mouse model of Tauopathy
Carvalho, K., Martin, E., Cès, A., Sarrazin, N., Lagouge-Roussey, P., Nous, C., Boucherit, L., Youssef, I., Prigent, A., Faivre, É., et al. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102139 · Cited by 54
Cary, G. A., Wiley, J. C., Gockley, J., Keegan, S., Amirtha Ganesh, S. S., Heath, L., Butler, R. R., Mangravite, L. M., Logsdon, B. A., Longo, F. M., et al. (2024) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12461 · Cited by 49
Neurodevelopmental Clues to Neurodegeneration
Schor, N. F., & Bianchi, D. W. (2021) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2021.07.012 · Cited by 49
Zhang, L. L., Hou, S., Movahedi, F., Li, Z., Li, L., Hu, J., Jia, Y., Huang, Y., Zhu, J., Sun, X., et al. (2023) · Nano Today · doi:10.1016/j.nantod.2023.101788 · Cited by 50
Toral-Rios, D., Long, J. M., Ulrich, J. D., Yu, J., Strickland, M. R., Han, X., Holtzman, D. M., Cashikar, A. G., & Paul, S. M. (2024) · Journal of Experimental Medicine · doi:10.1084/jem.20232000 · Cited by 47
KALRN: A central regulator of synaptic function and synaptopathies
Parnell, E., Shapiro, L. P., Voorn, R. A., Forrest, M. P., Jalloul, H. A., Loizzo, D. D., & Penzes, P. (2020) · Gene · doi:10.1016/j.gene.2020.145306 · Cited by 48
Pal, A., Rani, I., Pawar, A. T., Picozza, M., Rongioletti, M. C. A., & Squitti, R. (2021) · Biomolecules · doi:10.3390/biom11111598 · Cited by 48
Johnson, N. R., Yuan, P., Castillo, E., Lopez, T. P., Yue, W., Bond, A., Rivera, B. M., Sullivan, M. C., Hirouchi, M., Giles, K., et al. (2023) · Nature Communications · doi:10.1038/s41467-022-35753-w · Cited by 46
Shen, Z., Sun, D., Savastano, A., Varga, S. J., Cima‐Omori, M., Becker, S., Honigmann, A., & Zweckstetter, M. (2023) · Nature Communications · doi:10.1038/s41467-023-42295-2 · Cited by 46
Xia, Y., Sorrentino, Z. A., Kim, J. D., Strang, K. H., Riffe, C. J., & Giasson, B. I. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.010178 · Cited by 48
Long Non-coding RNA: Insight Into Mechanisms of Alzheimer's Disease
Lan, Z., Chen, Y., Jin, J., Xu, Y., & Zhu, X. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.821002 · Cited by 45
Cangalaya, C., Wegmann, S., Sun, W., Diez, L., Gottfried, A., Richter, K., Stoyanov, S., Pakan, J. M. P., Fischer, K., & Dityatev, A. E. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.02.023 · Cited by 48
C5aR1 signaling promotes region‐ and age‐dependent synaptic pruning in models of Alzheimer's disease
Gómez-Arboledas, Á., Fonseca, M. I., Kramár, E. A., Chu, S., Schartz, N. D., Selvan, P., Wood, M. A., & Tenner, A. J. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13682 · Cited by 47
Systemic inflammation induced the delayed reduction of excitatory synapses in the CA3 during ageing
Manabe, T., Rácz, I., Schwartz, S., Oberle, L., Santarelli, F., Emmrich, J. V., Neher, J. J., & Heneka, M. T. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15491 · Cited by 44
Microglia phagocytic mechanisms: Development informing disease
Beiter, R. M., Sheehan, P. W., & Schafer, D. P. (2024) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2024.102877 · Cited by 44
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Jennings, M. J., Kagiava, A., Vendredy, L., Spaulding, E. L., Stavrou, M., Hathazi, D., Grüneboom, A., Winter, V. D., Gess, B., Schara, U., et al. (2022) · Brain · doi:10.1093/brain/awac055 · Cited by 45
Knowing the enemy: strategic targeting of complement to treat Alzheimer disease
Tenner, A. J., & Petrisko, T. J. (2025) · Nature Reviews Neurology · doi:10.1038/s41582-025-01073-y · Cited by 49
PTEN activation contributes to neuronal and synaptic engulfment by microglia in tauopathy
Benetatos, J., Bennett, R. E., Evans, H. T., Ellis, S. A., Hyman, B. T., Bodea, L., & Götz, J. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02151-9 · Cited by 43
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Son, M. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00774-4 · Cited by 42
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Maccioni, R. B., Navarrete, L. P., González, A., González-Canacer, A., Guzmán‐Martínez, L., & Cortés, N. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191014 · Cited by 42
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Chen, T., Bosco, D. B., Ying, Y., Tian, D., & Wu, L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.616301 · Cited by 43
Kretzschmar, G. C., Bumiller‐Bini, V., Filho, M. A. G., Zonta, Y. R., Yu, K. S. T., de Souza, R. L. R., Dias‐Melicio, L. A., & Boldt, A. B. W. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.630869 · Cited by 42
Implication of type 4 NADPH oxidase (NOX4) in tauopathy
Luengo, E., Trigo-Alonso, P., Fernández‐Mendívil, C., Núñez, Á., del Campo, M., Porrero, C., García‐Magro, N., Negredo, P., Senar, S., Sánchez‐Ramos, C., et al. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.redox.2021.102210 · Cited by 44
Loss of forebrain BIN1 attenuates hippocampal pathology and neuroinflammation in a tauopathy model
Ponnusamy, M., Wang, S., Yuksel, M., Hansen, M. T., Blazier, D. M., McMillan, J. D., Zhang, X., Dammer, E. B., Collier, L. A., & Thinakaran, G. (2022) · Brain · doi:10.1093/brain/awac318 · Cited by 44
Liu, N., Liang, X., Chen, Y., & Xie, L. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102199 · Cited by 44
Deleterious Alteration of Glia in the Brain of Alzheimer’s Disease
Kim, E., Otgontenger, U., Jamsranjav, A., & Kim, S. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186676 · Cited by 42
Li, L., Liang, J., & Fu, H. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.10.020 · Cited by 42
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Kanmogne, M., & Klein, R. S. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.10.003 · Cited by 41
Targeting Complement C3a Receptor to Improve Outcome After Ischemic Brain Injury
Pekna, M., Stokowska, A., & Pekny, M. (2021) · Neurochemical Research · doi:10.1007/s11064-021-03419-6 · Cited by 41
Guo, Q., Li, Y., Xu, S., Wang, P., Qian, K., Yang, P., Sheng, D., Wang, L., Cheng, Y., Meng, R., et al. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.01.074 · Cited by 40
Glial cells and adaptive immunity in frontotemporal dementia with tau pathology
Hartnell, I. J., Blum, D. L., Nicoll, J. A. R., Dorothée, G., & Boche, D. (2020) · Brain · doi:10.1093/brain/awaa457 · Cited by 41
Schaler, A. W., Runyan, A. M., Clelland, C. L. T., Sydney, E. J., Fowler, S. L., Figueroa, H. Y., Shioda, S., Santa‐María, I., Duff, K., & Myeku, N. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.aba7394 · Cited by 41
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Chi, X., Yin, S., Sun, Y., Kou, L., Zou, W., Wang, Y., Jin, Z., Wang, T., & Xia, Y. F. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.09.022 · Cited by 42
Donison, N. S., Palik, J., Volkening, K., & Strong, M. J. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00842-z · Cited by 42
Barnett, D., Zimmer, T. S., Booraem, C., Palaguachi, F., Meadows, S. M., Xiao, H., Wong, M. Y., Luo, W., Gan, L., Chouchani, E. T., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01390-y · Cited by 41
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Camporesi, E., Lashley, T., Gobom, J., Lantero‐Rodriguez, J., Hansson, O., Zetterberg, H., Blennow, K., & Becker, B. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01119-4 · Cited by 43
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LeBlang, C. J., Medalla, M., Nicoletti, N. W., Hays, E. C., Zhao, J., Shattuck, J. E., Cruz, A. L., Wolozin, B. L., & Luebke, J. I. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00285 · Cited by 38
McKee, C., Hoffos, M., Vecchiarelli, H. A., & Tremblay, M. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1125982 · Cited by 38
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Stolero, N., & Frenkel, D. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15262 · Cited by 37
Synapse development is regulated by microglial THIK-1 K + channels
Izquierdo, P., Shiina, H., Hirunpattarasilp, C., Gillis, G., & Attwell, D. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2106294118 · Cited by 39
van der Ende, E. L., Heller, C., Sogorb‐Esteve, A., Swift, I. J., McFall, D. J., Peakman, G., Bouzigues, A., Poos, J. M., Jiskoot, L. C., Panman, J. L., et al. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02573-0 · Cited by 40
Li, Y., Yin, Q., Li, Q., Huo, A., Shen, T., Cao, J.-Q., Liu, C., Liu, T., Luo, W., & Cong, Q. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-023-01058-x · Cited by 36
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Robert, A., Schöll, M., & Vogels, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116132 · Cited by 37
Yednock, T. A., Fong, D. S., & Lad, E. M. (2022) · International Journal of Retina and Vitreous · doi:10.1186/s40942-022-00431-y · Cited by 35
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Howes, O., Marcinkowska, J., Turkheimer, F. E., & Carr, R. (2025) · Neuropsychopharmacology · doi:10.1038/s41386-024-01943-x · Cited by 34
Matera, A., Compagnion, A.-C., Pedicone, C., Kotah, J. M., Ivanov, A., Monsorno, K., Labouèbe, G., Leggio, L., Pereira-Iglesias, M., Beule, D., et al. (2025) · Immunity · doi:10.1016/j.immuni.2024.11.003 · Cited by 34
Sokolova, D., Childs, T., & Hong, S. Y. (2021) · Faculty Reviews · doi:10.12703/r/10-19 · Cited by 35
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Song, W., Li, Q., Wang, T., Li, Y., Fan, T., Zhang, J., Wang, Q., Pan, J., Dong, Q., Sun, Z. S., et al. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.02.027 · Cited by 36
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Brody, A. H., Nies, S. H., Guan, F., Smith, L. M., Mukherjee, B., Salazar, S. A., Lee, S., Lam, T. K. T., & Strittmatter, S. M. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00526-y · Cited by 36
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Qin, Q., Wang, M., Yin, Y., & Tang, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.845897 · Cited by 34
de Soysa, Y., Therrien, M., Walker, A. C., & Stevens, B. (2022) · Seminars in Immunology · doi:10.1016/j.smim.2022.101651 · Cited by 34
Chen, Y., Chu, J. M. T., Wong, G. T. C., & Chang, R. C. (2024) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-024-10107-z · Cited by 32
Wang, C., Chang, Y., Zhu, J., Wu, Y., Jiang, X., Zheng, S., Li, G., & Ma, R. (2023) · Experimental Neurology · doi:10.1016/j.expneurol.2023.114355 · Cited by 32
Zhou, A., Cheng, H., Liu, H., Li, L., Chen, Z., Chen, S., Wang, C., & Wang, D. (2023) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2023.121033 · Cited by 31
Pampuščenko, K., Morkūnienė, R., Krasauskas, L., Smirnovas, V., Brown, G. C., & Borutaitė, V. (2023) · Scientific Reports · doi:10.1038/s41598-023-37887-3 · Cited by 31
The activation of microglia by the complement system in neurodegenerative diseases
Zhao, H., Lv, Y., Xu, J., Song, X., Wang, Q., Zhai, X., Ma, X., Qiu, J., Cui, L., & Sun, Y. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102636 · Cited by 32
Paskus, J. D., Tian, C., Fingleton, E., Shen, C., Chen, X., Li, Y., Myers, S. A., Badger, J. D., Bemben, M. A., Herring, B. E., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.10.115 · Cited by 31
Precision Medicine in Neurology: The Inspirational Paradigm of Complement Therapeutics
Gavriilaki, M., Kimiskidis, V. Κ., & Gavriilaki, E. (2020) · Pharmaceuticals · doi:10.3390/ph13110341 · Cited by 32
Trilobatin Alleviates Cognitive Deficits and Pathologies in an Alzheimer’s Disease Mouse Model
Ding, J., Huang, J. V., Yin, D., Liu, T., Ren, Z., Hu, S., Le, C., Le, C., Zhou, H., Zhu, L., et al. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/3298400 · Cited by 31
Metadata
- Authors
- Dejanovic, B., Huntley, M. A., De Mazière, A., Meilandt, W. J., Wu, T., Srinivasan, K., Jiang, Z., Gandham, V., Friedman, B. A., Ngu, H., Foreman, O., Carano, R. A. D., Chih, B., Klumperman, J., Bakalarski, C., Hanson, J. E., & Sheng, M.
- Affiliations
- Genentech (US)
- Utrecht University (NL)
- Corresponding author
- Dejanovic, Borislav
- Sheng, Morgan
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 100
- Issue
- 6
- Pages
- 1322-1336.e7
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2898757824
- Semantic Scholar
- 317f16e04c2c13a66baa96bdf9b7e396f626ccf7
- Cited by
- 517
- References
- 79
- Citations by year
- 2026: 61 · 2025: 56 · 2024: 73 · 2023: 67 · 2022: 74 · 2021: 83 · 2020: 65 · 2019: 33 · 2018: 3
- FWCI
- 18.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- tauopathy, synaptic loss, postsynaptic density, C1q, microglia, dendritic spines, actin cytoskeleton, phosphorylated tau, Alzheimer's disease, synaptic proteome
- MeSH terms
- Prion Proteins, Animals, Animals, Newborn, Antibodies, Cell Differentiation, Cells, Cultured, Embryo, Mammalian, Female, Humans, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Synapses, Complement C1q, Amyloid beta-Protein Precursor, tau Proteins, Proteome, Tauopathies, Mice, Rats, Presenilin-2, Induced Pluripotent Stem Cells, Post-Synaptic Density
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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