The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy
Open accessAbstract
APOE4 is the strongest genetic risk factor for late-onset Alzheimer disease. ApoE4 increases brain amyloid-β pathology relative to other ApoE isoforms. However, whether APOE independently influences tau pathology, the other major proteinopathy of Alzheimer disease and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human ApoE knock-in (KI) or ApoE knockout (KO) background, here we show that P301S/E4 mice have significantly higher tau levels in the brain and a greater extent of somatodendritic tau redistribution by three months of age compared with P301S/E2, P301S/E3, and P301S/EKO mice. By nine months of age, P301S mice with different ApoE genotypes display distinct phosphorylated tau protein (p-tau) staining patterns. P301S/E4 mice develop markedly more brain atrophy and neuroinflammation than P301S/E2 and P301S/E3 mice, whereas P301S/EKO mice are largely protected from these changes. In vitro, E4-expressing microglia exhibit higher innate immune reactivity after lipopolysaccharide treatment. Co-culturing P301S tau-expressing neurons with E4-expressing mixed glia results in a significantly higher level of tumour-necrosis factor-α (TNF-α) secretion and markedly reduced neuronal viability compared with neuron/E2 and neuron/E3 co-cultures. Neurons co-cultured with EKO glia showed the greatest viability with the lowest level of secreted TNF-α. Treatment of P301S neurons with recombinant ApoE (E2, E3, E4) also leads to some neuronal damage and death compared with the absence of ApoE, with ApoE4 exacerbating the effect. In individuals with a sporadic primary tauopathy, the presence of an ε4 allele is associated with more severe regional neurodegeneration. In individuals who are positive for amyloid-β pathology with symptomatic Alzheimer disease who usually have tau pathology, ε4-carriers demonstrate greater rates of disease progression. Our results demonstrate that ApoE affects tau pathogenesis, neuroinflammation, and tau-mediated neurodegeneration independently of amyloid-β pathology. ApoE4 exerts a 'toxic' gain of function whereas the absence of ApoE is protective.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“The early p-Tau staining types 1 and 2 were enriched in PS19-E3 mice (Fig. 1h), as seen previously7.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [7]
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
“In addition, APOE4 was found to reduce the phagocytosis ability of glial cells, enhance microglia proinflammatory activation by Aβ plaques or tau aggregates and promote neurodegeneration in the mouse models.176,177”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [176]
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
“previous studies have demonstrated that deletion of Apoe and overexpression of Ldlr can reduce tau‐associated neurodegeneration.”
From Deletion of neuronal Idol ameliorates Alzheimer's disease–related pathologies via APOE receptors (2025) · 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 previous studies, brain regions of P301S: APOE4 -KI mice demonstrate marked neurodegeneration compared to P301S: APOE3 -KI mice at 9.5 months of age, although the MGnD phenotype was similar between the two groups 12,21 .”
From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [21]
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
“Sample sizes were chosen based on prior publications using the APP/PS1 and P301S mouse models, which provided estimations of expected effect sizes and variance.”
From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as Shi et al., 2017
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
“ApoE has been shown to independently influence several key factors that drive pathogenesis of AD, including 𝛃 -amyloidosis, tauopathy, and synaptic dysfunction (1-3).”
From Therapeutic Idol reduction ameliorates amyloidosis and improves cognitive function in APP/PS1 mice (2020) · cites this paper as [3]
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
“Reducing ApoE levels is generally protective in AD models1,4–6.”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [6]
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
“It exacerbates AD-related pathologies, including amyloid-beta (Aβ) plaques, Tau tangles, neurodegeneration and neuroinflammation4–16.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [7]
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
“PS19-E4 mice displayed roughly two-fold higher AT8+ p-Tau coverage area than PS19-E3 mice (Fig. 1b,c), as reported previously7,55.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [7]
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 10-month-old PS19-E4 mice, the AT8 (p-Tau) percent coverage area was negatively correlated with hippocampal volume (Fig. 4f), as shown previously7,55, indicating a deleterious role of p-Tau in hippocampal degeneration.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [7]
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
“PS19-E4 mice exhibited significantly reduced hippocampal volume compared to WT and PS19-E3 mice (Fig. 4a,b and Extended Data Fig. 2a), as reported previously7,55.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [7]
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
“while APOE2 or Apoe KO protects against, and APOE4 exacerbates, tauopathy-induced neurodegeneration [29].”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [29]
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
“APOE is a lipid transporter expressed in astrocytes and microglia and has been shown to affect microglial functions including neuroinflammation and phagocytosis7–9.”
From The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway (2025) · cites this paper as [9]
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
“Moreover, APOE4 exacerbates tau-induced neurodegeneration, partially attributed to a critical immune hub that involves IFN-driven microglial activation and interaction with cytotoxic T cells64,65.”
From The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway (2025) · cites this paper as [64]
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
“That interpretation is consistent with prior human genetics 5 , with biochemical data mapping lipid binding and oligomerization properties of ApoE to its C-terminal domain and with other data linking the physical state of ApoE to its role in amyloid handling, tau-mediated neurodegeneration 15 and receptor-dependent trafficking 16 .”
From Association of Rare APOE Missense Variants R189C and W276C With Risk of Alzheimer Disease (2026) · cites this paper as [15]
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
“Specifically, in a tauopathy mouse model (PS19, overexpressing the MAPT P301S mutation) crossed with APOE-targeted replacement mice (Box 3), APOE had a marked isoform-dependent effect on tau pathology in the absence of Aβ plaques, with APOE4/PS19 mice showing the greatest extent of tau neurofibrillary tangle pathology and neuronal loss and APOE2/PS19 mice the lowest127 (Fig. 2f).”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [127]
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
“APOE is a lipid transporter expressed on astrocytes and microglia and has been shown to affect numerous microglial functions including neuroinflammation and phagocytosis8–10.”
From APOE3 - R136S mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition (2024) · cites this paper as [10]
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
“Moreover, APOE4 greatly exacerbates tau-induced neurodegeneration, partially attributed to a critical immune hub that involves IFN-driven microglial activation and interaction with cytotoxic T cells60,61.”
From APOE3 - R136S mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition (2024) · cites this paper as [60]
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
“ApoE ablation in P301S tau transgenic (Tg) mice markedly reduced brain atrophy and tau pathology compared to the presence of apoE, whereas apoE4 significantly exacerbated neurodegeneration compared to apoE2 and apoE3 (Shi et al., 2017).”
From Overexpressing low‐density lipoprotein receptor reduces tau‐associated neurodegeneration in relation to apoE‐linked mechanisms (2021) · cites this paper as Shi et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“several in vivo studies of E4 mice and humans show an exaggerated response to inflammation in E4 individuals (Vitek et al., 2009; Shi et al., 2017; Zhu et al., 2012; Gale et al., 2014).”
From APOE4 reshapes the lipid droplet proteome and modulates microglial inflammatory responses (2025) · cites this paper as Shi et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“By 9.5 mo of age, PS19 mice manifested marked microgliosis and astrogliosis, which have been associated with tau phosphorylation and neurodegeneration (Yoshiyama et al., 2007; Shi et al., 2017).”
From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Shi et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The area of Iba1 and CD68 immunoreactivity was significantly elevated in T mice in agreement with previously published results (Shi et al., 2017).”
From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Shi et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Deficiency of Apoe or Trem2 attenuates tau-dependent neuroinflammation and neurodegeneration in mice expressing human P301S mutant tau (PS19 mice) (Shi et al., 2017; Leyns et al., 2017; Sayed et al., 2018).”
From Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy (2024) · cites this paper as Shi et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Lower levels of pTau and reduced pTau deposition correlate with less neurodegeneration (Shi et al., 2017).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Shi et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Microglia play a crucial role in tau pathology and tau-mediated neurodegeneration. Neuroinflammation is one of the hallmarks of tauopathy-linked neurodegeneration, and microglia are a major driving force for this biological process (Shi et al., 2017; Yoshiyama 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 Shi et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Numerous human and rodent model studies have highlighted the important role of astrocytes in AD and tau pathology, with astrocyte activation occurring prior to large scale NFT formation, synaptic dysfunction, and neuronal loss (Bussian et al., 2018; Shi et al., 2017; Yoshiyama 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 Shi et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Microglia play a crucial role in tau pathology and tau-mediated neurodegeneration. Neuroinflammation is one of the hallmarks of tauopathy-linked neurodegeneration, and microglia are a major driving force for this biological process (Shi et al., 2017; Yoshiyama 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 Shi et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This further supports a potentially dichotomous role for microglial responses, with Apoe and Trem2-dependent functions being protective in response to amyloid, but harmful in the presence of intracellular tau pathology (Gratuze et al., 2020; Shi et al., 2017; Ulrich 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 Shi et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Genetic deletion of astrocytic APOE4 but not APOE3 was significantly neuroprotective in P301S Tau mice; however, it should be noted that crossing P301S Tau mice to Apoe KO mice or eliminating microglia resulted in no significant evidence of neurodegeneration/brain volume loss by 9 months of age relative to non-Tau transgenic mice (Shi et al., 2019; Shi et al., 2017).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Shi et al., 2017
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Further, global knockout of ApoE also very strongly suppresses neurodegeneration and knockout of APOE4 from astrocytes also strongly attenuates tau-mediated degeneration [92, 106].”
From ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer’s disease and related disorders (2026) · cites this paper as [92]
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
“as evidenced by studies showing astrocyte-specific knockout of ApoE results in markedly decreased Aβ pathology and tau-mediated neurodegeneration (13, 14, 15).”
From Lipidome and proteome of astrocyte and microglia ApoE lipoprotein reveal differences based on cell type and ApoE isoform (2026) · cites this paper as [13]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“APOE4 is associated with increased amyloid-β deposition, hyperphosphorylation and aggregation of tau, and accelerated cognitive decline4–7.”
From APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes (2022) · cites this paper as [5]
The cited source says what the claim attributes to it.
In the citing paper
“While it has not been demonstrated yet that ApoE variants impact neuron loss in APP transgenic mice, an exacerbation of the neurodegenerative phenotype has been reported in a Tau transgenic model bred on a human ApoE4 genetic background [144].”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [144]
The cited source says what the claim attributes to it.
In the citing paper
“For example, in a tauopathy mouse model, Apoe KO mice exhibited less tau‐mediated neurodegeneration compared to those expressing APOE3 or APOE4.”
From Deletion of neuronal Idol ameliorates Alzheimer's disease–related pathologies via APOE receptors (2025) · cites this paper as [75]
The cited source says what the claim attributes to it.
In the citing paper
“ApoE also markedly accelerates amyloid deposition (23,24) as well as taumediated neurodegeneration in mouse models (25).”
From Regulation of astrocyte lipid metabolism and ApoE secretion by the microglial oxysterol, 25-hydroxycholesterol (2023) · cites this paper as [25]
The cited source says what the claim attributes to it.
In the citing paper
“Neurodegeneration is a pathological hallmark of AD 20 , which is exacerbated in a mouse model of tauopathy expressing APOE4 (refs. 12,21).”
From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [21]
The cited source says what the claim attributes to it.
In the citing paper
“suggesting the contribution of astrocytosis to hippocampal degeneration, as reported previously7”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“suggesting the contribution of microgliosis to hippocampal degeneration, as reported in previous studies7,55”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“APOE4 exacerbates these phenotypes in a PS19 tauopathy model7,11,55.”
From The APOE-R136S mutation protects against APOE4-driven tau pathology, neurodegeneration, and neuroinflammation (2023) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“Conversely, the microglial response to tauopathy appears to drive neurodegeneration.”
From APOE Christchurch enhances a disease-associated microglial response to plaque but suppresses response to tau pathology (2025) · cites this paper as [29]
The cited source says what the claim attributes to it.
In the citing paper
“Importantly, Apoe knockout/PS19 mice were relatively spared from any neuronal and hippocampal volume loss when compared with any of the APOE-expressing mice, despite similar levels of tau accumulation compared with APOE3/PS19 mice127.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [127]
The cited source says what the claim attributes to it.
In the citing paper
“ApoE ablation in P301S tau transgenic (Tg) mice markedly reduced brain atrophy and tau pathology compared to the presence of apoE, whereas apoE4 significantly exacerbated neurodegeneration compared to apoE2 and apoE3 (Shi et al., 2017).”
From Overexpressing low‐density lipoprotein receptor reduces tau‐associated neurodegeneration in relation to apoE‐linked mechanisms (2021) · cites this paper as Shi et al., 2017
The cited source says what the claim attributes to it.
In the citing paper
“APOE4 also increases pTau levels and promotes tau pathology in mice (Shi et al., 2017).”
From APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice (2026) · cites this paper as Shi et al., 2017
The cited source says what the claim attributes to it.
In the citing paper
“Previous studies have demonstrated that APOE4 exacerbates tau pathology in PS19 mice (Shi et al., 2017)”
From APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice (2026) · cites this paper as Shi et al., 2017
The cited source says what the claim attributes to it.
In the citing paper
“Our previous work showed a higher innate immune reactivity of apoE4-expressing microglia following LPS treatment and found that APOE4/4 genotype greatly influences tau-dependent neuroinflammation in a tau transgenic mouse model of neurodegeneration [43].”
From 25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner (2020) · cites this paper as [43]
The cited source says what the claim attributes to it.
In the citing paper
“we found that TE4 mice, an aggressive mouse model showing the strongest brain neurodegeneration and neuroinflammation [43], express significantly higher levels of CH25H mRNA than TEKO mice (Fig. 1 g).”
From 25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner (2020) · cites this paper as [43]
The cited source says what the claim attributes to it.
In the citing paper
“as well as in three mouse models of AD pathology; APP/PS1 transgenic mice, tau transgenic mice (PS19) and a recently described APOE4xP301S (TE4) tau transgenic mouse model of accelerated tau pathology and neurodegeneration [43].”
From 25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner (2020) · cites this paper as [43]
The cited source says what the claim attributes to it.
In the citing paper
“APOE-TR mice exhibit APOE genotype-dependent effects on Aβ seeding, Aβ clearance and tau-dependent neurodegeneration when crossed with APP or MAPT mutant mice (Holtzman et al., 2000; Shi et al., 2017).”
From Cholesterol and matrisome pathways dysregulated in astrocytes and microglia (2022) · cites this paper as Shi et al., 2017
The cited source says what the claim attributes to it.
In the citing paper
“Specifically, the expression of apoE4 resulted in a significant increase in the loss of neurons, brain volume, and glial inflammatory responses compared to other apoE isoforms, while the absence of apoE throughout life alleviated neurodegeneration and inflammation.”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Shi et al., 2017
The cited source says what the claim attributes to it.
In the citing paper
“Since apoE4 strongly exacerbates tauopathy and tau-mediated neurodegeneration in P301S Tau transgenic mice and the absence of apoE throughout life abrogates the majority of the severe brain damage that occurs in this model, we sought to understand the role of apoE3 and apoE4 produced by astrocytes (Shi et al., 2019; Shi et al., 2017).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Shi et al., 2017
The cited source says what the claim attributes to it.
In the citing paper
“P301S Tau transgenic mice with human APOE4 knocked-in develop significantly more hippocampal and entorhinal cortex/piriform cortex (EC/PC) volume loss than APOE3-expressing mice at this age (Shi et al., 2017).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Shi et al., 2017
The cited source says what the claim attributes to it.
In the citing paper
“The amount of astrogliosis is also highly correlated with mouse brain volume in a mouse model of tauopathy (Shi et al., 2017).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Shi et al., 2017
The cited source says what the claim attributes to it.
In the citing paper
“Since apoE4 strongly exacerbates tauopathy and tau-mediated neurodegeneration in P301S Tau transgenic mice and the absence of apoE throughout life abrogates the majority of the severe brain damage that occurs in this model, we sought to understand the role of apoE3 and apoE4 produced by astrocytes (Shi et al., 2019; Shi et al., 2017).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Shi et al., 2017
The cited source says what the claim attributes to it.
In the citing paper
“Further, global knockout of ApoE also very strongly suppresses neurodegeneration and knockout of APOE4 from astrocytes also strongly attenuates tau-mediated degeneration [92, 106].”
From ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer’s disease and related disorders (2026) · cites this paper as [92]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Consistent with APOE’s biological function2–6, APOE4 significantly altered signaling pathways associated with cholesterol homeostasis and transport.”
From APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes (2022) · cites this paper as [5]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“In previous studies, brain regions of P301S: APOE4 -KI mice demonstrate marked neurodegeneration compared to P301S: APOE3 -KI mice at 9.5 months of age, although the MGnD phenotype was similar between the two groups 12,21 .”
From APOE4 impairs the microglial response in Alzheimer’s disease by inducing TGFβ-mediated checkpoints (2023) · cites this paper as [21]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Mutations in ApoE that reduce binding to LDLR, namely ApoE2, but also to HSPG and LRP1, like the APOE Christchurch variant, also decrease tau seeding in wildtype mice and in the context of Aβ pathology [91, 92].”
From ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer’s disease and related disorders (2026) · cites this paper as [92]
Experimental — accuracy not yet measuredIn the citing paper
“supports recent evidence that tau may play an early pathological role in Alzheimer’s disease129–131”
From Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (2019) · cites this paper as [130]
In the citing paper
“Studies have demonstrated that APOE4 drives Aβ- and tau-mediated neurodegeneration by inducing microglial and astrocytic activation.174–179”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [175]
In the citing paper
“APOE4 significantly aggravated tau-mediated neurodegeneration in a tauopathy mouse model and induced tau aggregates in brain, while genetic ablation of APOE attenuated tau-induced neurodegeneration [469, 470].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [469]
In the citing paper
“ApoE4 affects neuroinflammation, tau pathology, and tau-mediated neurodegeneration independently of Aβ pathology [143].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [143]
In the citing paper
“In a recent study assessing the effect of ApoE-TR in the PS19 (tauP301S) tauopathy mouse model, ApoE4 dramatically exacerbated tau-mediated neurodegeneration”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Shi et al., 2017
In the citing paper
“Multiple studies employing ApoE genetic deletion (Bales et al., 1999; Verghese et al., 2013), conditional expression of ApoE isoforms (Liu et al., 2017) or ASO-mediated knockdown of ApoE expression (Huynh et al., 2017b) suggest that lowering ApoE levels reduces relevant pathology in both amyloidosis and tauopathy mouse models (Shi et al., 2017).”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Shi et al., 2017
In the citing paper
“Interestingly, knocking-out apoE (apoE-KO) protected the mice from Tau-P301S-induced neurodegeneration and neuroinflammation.”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [80]
In the citing paper
“These data strongly support apoE4’s gain of toxic effects on tau pathology and its related neurodegeneration and neuroinflammation, all of which are independent of Aβ [80].”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [80]
In the citing paper
“In mutant human Tau-P301S transgenic mice, expression of apoE4 led to more advanced tau pathology, brain atrophy, and neuroinflammation.”
From Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer’s disease (2019) · cites this paper as [80]
In the citing paper
“In the tau model of neurodegeneration, genetic deletion of either Apoe or Trem2 also arrested neurodegeneration, demonstrating that this pathway negatively regulates the homeostatic signature182,183.”
From Microglial signatures and their role in health and disease (2018) · cites this paper as [182]
In the citing paper
“References 182 and 183 connect TREM2 and ApoE signalling with exacerbation of neuroinflammation and tauopathy.”
From Microglial signatures and their role in health and disease (2018) · cites this paper as [182]
In the citing paper
“However, astrocytes are immune-competent. They respond to a wide range of brain insults and are activated in a wide range of neurodegenerative diseases including Alzheimer’s disease9,69–71.”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [69]
In the citing paper
“Notably, genetic ablation of ApoE in various neurodegenerative mouse models — including tauopathy69, synucleinopathy106, and experimental autoimmune encephalomyelitis (EAE)107 — shows a similar protective effect against neurodegeneration and disease severity”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [69]
In the citing paper
“In a tauopathy mouse model, genetic ablation of ApoE markedly reduces activation of microglia and astrocytes activation and ameliorates brain atrophy69.”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [69]
In the citing paper
“we recently reported that ApoE4 exacerbated tau pathogenesis and tau-mediated neurodegeneration relative to other ApoE isoforms independent of amyloid-β69.”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [69]
In the citing paper
“Contrary to LPS treatment where ApoE deletion amplifies the immune response, under neurodegenerative or neuroinflammatory conditions, ApoE deficiency attenuates inflammation28,69,97,107 and disease severity69,106,107.”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [69]
In the citing paper
“We recently found that human ApoE4 expressed under the endogenous murine ApoE promoter exacerbates tau pathology compared to other ApoE isoforms in a tauopathy mouse model independent of amyloid-β pathology69.”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [69]
In the citing paper
“ApoE4 significantly exacerbates neurodegeneration whereas ApoE ablation strongly attenuates the damage compared to the presence of ApoE regardless of ApoE isoforms69.”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [69]
In the citing paper
“This study demonstrates an amyloid-β-independent role of ApoE in regulating neurodegeneration and neuroinflammation in the setting of a tauopathy.”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [69]
In the citing paper
“The protective effect of ApoE deficency on neurodegeneration is in line with that of TREM2.”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [69]
In the citing paper
“Nonetheless, the inheritance of the ε4 allele of the Apolipoprotein (APO) E gene, which is associated with both increased Aβ deposition and tau pathology (Shi et al., 2017; Shi et al., 2021), constitutes the strongest genetic risk factor for sporadic AD, determining the age at onset of the disease and strictly influencing its progression (Cerf et al., 2011; Hashimoto et al., 2012; Koffie et al., 2”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Shi et al., 2017
In the citing paper
“In addition, we have reported in mouse studies that apoE isoforms directly affect tauopathy and tau-mediated neurodegeneration in P301S tau transgenic mice expressing different human apoE isoforms (Shi et al., 2017).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Shi et al., 2017
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971
Self-citationStrittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268
Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores
Liu, X., Zhang, Z., Ruan, J., Pan, Y., Magupalli, V. G., Wu, H., & Lieberman, J. (2016) · Nature · doi:10.1038/nature18629 · Cited by 3,202
Hyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092
Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.3.631 · Cited by 2,668
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543
Self-citationGenomic analysis of reactive astrogliosis
Zamanian, J. L., Xu, L., Foo, L. C., Nouri, N., Zhou, L., Giffard, R. G., & Barres, B. A. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.6221-11.2012 · Cited by 2,404
Self-citationSynapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208
TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques
Wang, Y., Ulland, T. K., Ulrich, J. D., Song, W., Tzaferis, J. A., Hole, J. T., Yuan, P., Mahan, T. E., Shi, Y., Gilfillan, S., et al. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20151948 · Cited by 840
Self-citationYuan, P., Condello, C., Keene, C. D., Wang, Y., Bird, T. D., Paul, S. M., Luo, W., Colonna, M., Baddeley, D., & Grutzendler, J. (2016) · Neuron · doi:10.1016/j.neuron.2016.05.003 · Cited by 817
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 701–800 of 1,006
Yoshida, K., Hata, Y., Ichimata, S., & Nishida, N. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190196 · Cited by 14
Dai, D., Tropea, T. F., Robinson, J. L., Suh, E. R., Hurtig, H. I., Weintraub, D. A., Deerlin, V. M. V., Lee, E. B., Trojanowski, J. Q., & Chen‐Plotkin, A. S. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02199-7 · Cited by 14
Gao, H., Zheng, W., Li, C., & Xu, H. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111582 · Cited by 14
Translational cognitive systems: focus on attention
Roberts, B. Z., & Young, J. W. (2022) · Emerging Topics in Life Sciences · doi:10.1042/etls20220009 · Cited by 14
Alzheimer’s Disease and Impaired Bone Microarchitecture, Regeneration and Potential Genetic Links
Zhang, M., Hu, S., & Sun, X. (2023) · Life · doi:10.3390/life13020373 · Cited by 15
Apolipoprotein ε in Brain and Retinal Neurodegenerative Diseases
Abyadeh, M., Gupta, V., Paulo, J. A., Sheriff, S., Shadfar, S., Fitzhenry, M. J., Amirkhani, A., Gupta, V. B., Salekdeh, G. H., Haynes, P. A., et al. (2023) · Aging and Disease · doi:10.14336/ad.2023.0312-1 · Cited by 15
González-Mundo, I., Pérez-Vielma, N. M., Gómez‐López, M., Fleury, A., Correa‐Basurto, J., Rosales‐Hernández, M. C., Sixto‐López, Y., Martínez–Godínez, M. D. L. Á., Domínguez‐López, A., & Miliar-García, Á. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.110951 · Cited by 14
Yang, M., Tan, H. L. E., Zhang, K., Lian, N., Yu, Y., & Yu, Y. (2020) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.10041 · Cited by 14
Kurakin, A. V., & Bredesen, D. E. (2020) · Aging · doi:10.18632/aging.103883 · Cited by 15
Behavioral and biologic characteristics of cancer-related cognitive impairment biotypes
Mulholland, M. M., Prinsloo, S., Kvale, E. A., Dula, A. N., Palesh, O. G., & Kesler, S. R. (2023) · Brain Imaging and Behavior · doi:10.1007/s11682-023-00774-6 · Cited by 13
Tan, R., Hong, R., Sui, C., Yang, D., Tian, H., Zhu, T., & Yang, Y. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1233762 · Cited by 13
Lan, G., Du, J., Chen, X., Wang, Q., Han, Y., & Guo, T. (2023) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2023.09.012 · Cited by 15
Alzheimer's disease approaches - Focusing on pathology, biomarkers and clinical trial candidates
Hroudová, J., & Fišar, Z. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2024.111069 · Cited by 13
Brandão, W. N., Jain, N., Yin, Z., Kleemann, K. L., Carpenter, M., Bao, X., Serrano, J. R., Tycksen, E., Durão, A. C. C. D. S., Barry, J., et al. (2025) · Science Translational Medicine · doi:10.1126/scitranslmed.adk3690 · Cited by 13
Self-citationMak, E., Reid, R. I., Przybelski, S. A., Fought, A. J., Lesnick, T. G., Schwarz, C. G., Senjem, M. L., Raghavan, S., Vemuri, P., Jack, C. R., et al. (2025) · npj Parkinson s Disease · doi:10.1038/s41531-025-00944-x · Cited by 13
Liang, J., Li, R., Wong, G., & Huang, X. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00879-0 · Cited by 13
Holmes, B. B., Weigel, T. K., Chung, J. M., Kaufman, S. K., Apresa, B. I., Byrnes, J. R., Kumru, K. S., Vaquer‐Alicea, J., Gupta, A., Rose, I. V. L., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00883-4 · Cited by 14
Self-citationWhen time's arrow doesn't bend: APOE-ε4 influences episodic memory before old age
Eich, T. S., Tsapanou, A., & Stern, Y. (2019) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2019.107180 · Cited by 13
Microglia at the Centre of Brain Research: Accomplishments and Challenges for the Future
Soares, N. L., & Vieira, H. L. A. (2021) · Neurochemical Research · doi:10.1007/s11064-021-03456-1 · Cited by 14
Tau aggregation and its relation to selected forms of neuronal cell death
Tolkovsky, A. M., & Spillantini, M. G. (2021) · Essays in Biochemistry · doi:10.1042/ebc20210030 · Cited by 13
Functional insight into LOAD-associated microglial response genes
Jonas, L. A., Jain, T., & Li, Y. (2022) · Open Biology · doi:10.1098/rsob.210280 · Cited by 13
Belonwu, S., Li, Y., Bunis, D. G., Rao, A. A., Solsberg, C. W., Oskotsky, T., Taubes, A. L., Grone, B. P., Zalocusky, K. A., Fragiadakis, G. K., et al. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.749991 · Cited by 13
Fleeman, R. M., Snyder, A. M., Kuhn, M. K., Chan, D. C., Smith, G. C., Crowley, N. A., Arnold, A. C., & Proctor, E. A. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.11.015 · Cited by 13
He, M., Liu, Z., Lian, T., Guo, P. F., Zhang, W., Huang, Y. M., Zhang, Y., Liu, G., Zhang, W., Li, J., et al. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14560 · Cited by 13
Koller, E. J., Cruz, E. G. D. L., Weinrich, M. J., Williams, T., Cruz, P. E., Ryu, D. H., Golde, T. E., Sullivan, P. M., Lewis, J. M., Borchelt, D., et al. (2020) · Molecular Neurobiology · doi:10.1007/s12035-019-01859-4 · Cited by 13
Self-citationHellstrøm, T., Anđelić, N., Holthe, Ø. Ø., Helseth, E., Server, A., Eiklid, K. L., & Sigurðardóttir, S. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.735206 · Cited by 14
Peripheral immune and metabolic regulation of Aβ and Tau by exercise in Alzheimer’s disease
Yu, Y., & Chen, K. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1678526 · Cited by 14
Takamatsu-Yukawa, K., Yamamoto-Mcguire, S., Cafaro, L., Hong, C., Kamme, F., Ikezu, T., & Ikezu, S. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01661-3 · Cited by 12
DNA methylation patterns of FKBP5 regulatory regions in brain and blood of humanized mice and humans
Yusupov, N., Roeh, S., Elliott, L. S., Chang, S., Loganathan, S., Urbina-Treviño, L., Fröhlich, A. S., Sauer, S., Ködel, M., Matosin, N., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02430-x · Cited by 13
Paiva, I., Séguin, J., Grgurina, I., Singh, A. K., Cosquer, B., Plassard, D., Tzeplaeff, L., Gras, S. L., Cotellessa, L., Decraene, C., et al. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106538 · Cited by 12
Yang, X., Yao, K., Zhang, M., Zhang, W., & Zu, H. (2025) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2025.111321 · Cited by 12
Giorgio, J., Jonson, C., Wang, Y., Yokoyama, J. S., Wang, J., Jagust, W. J., & Initiative, O. B. O. T. A. D. N. (2025) · Nature Communications · doi:10.1038/s41467-025-60370-8 · Cited by 14
Ma, Y., Wang, Y., Tan, L., Xu, W., Shen, X., Wang, H.-F., Hou, X., Cao, X., Bi, Y., Dong, Q., et al. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201426 · Cited by 13
Network dysfunction in cognitively normal APOE ε4 carriers is related to subclinical tau
Butt, O. H., Meeker, K. L., Wisch, J. K., Schindler, S. E., Fagan, A. M., Benzinger, T. L. S., Cruchaga, C., Holtzman, D. M., Morris, J. C., & Ances, B. M. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12375 · Cited by 12
Self-citationGenome-wide association study identifies APOE locus influencing plasma p-tau181 levels
Huang, Y., Yang, Y., Wang, H.-F., Shen, X., Tan, L., Yu, J., & Initiative, A. D. N. (2022) · Journal of Human Genetics · doi:10.1038/s10038-022-01026-z · Cited by 12
Self-citationThe Strategies for Treating “Alzheimer’s Disease”: Insulin Signaling May Be a Feasible Target
You, G., Yao, J., Liu, Q., & Li, N. (2022) · Current Issues in Molecular Biology · doi:10.3390/cimb44120421 · Cited by 12
Li, S., Roy, E. R., Wang, Y., Watkins, T. A., & Cao, W. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03720-1 · Cited by 14
APOE ɛ4 exacerbates age-dependent deficits in cortical microstructure
Mak, E., Dounavi, M., Operto, G., Ziukelis, E. T., Jones, P. S., Low, A., Swann, P., Newton, C., Terrera, G. M., Malhotra, P., et al. (2023) · Brain Communications · doi:10.1093/braincomms/fcad351 · Cited by 13
Neuroinflammation drives APOE genotype-dependent differential expression of neprilysin
Graykowski, D. R., Kasparian, K., Caniglia, J. L., Gritsaeva, Y., & Cudaback, E. (2020) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2020.577315 · Cited by 12
Industrial pollution with copper and other heavy metals in a beef cattle ranch.
Parada, R. P., González, S., & Bergqvist, E. (1987) · PubMed · Cited by 12
Teter, B., Campagna, J. J., Zhu, C., McAuley, G. E., Spilman, P. R., Kohn, D. B., & John, V. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.23.590784 · Cited by 12
Genetics of progressive supranuclear palsy in a Chinese population
Xiao, X., Yang, Q., Wen, Y., Jiao, B., Liao, X., Zhou, Y., Weng, L., Liu, H., Xu, T., Zhu, Y., et al. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105819 · Cited by 11
Emmerson, J. T., Malcolm, J. C., Carmo, S. D., Nguyen, P., Breuillaud, L., Martínez-Trujillo, J., & Cuello, A. C. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106317 · Cited by 11
Rubinski, A., Dewenter, A., Zheng, L., Franzmeier, N., Stephenson, H. G., Deming, Y. K., Duering, M., Gesierich, B. G., Denecke, J., Pham, A.-V., et al. (2023) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-023-06530-8 · Cited by 11
Self-citationEarly CA2 Tau Inclusions Do Not Distinguish an Age-Related Tauopathy from Early Alzheimer’s Disease
Tredici, K. D., Schön, M., Feldengut, S., Ghebremedhin, E., Kaufman, S. K., Wiesner, D., Roselli, F., Mayer, B., Amunts, K., & Braak, H. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-240483 · Cited by 11
Perdaens, O., & Pesch, V. V. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312637 · Cited by 12
Tau Accumulation Induces Microglial State Alterations in Alzheimer's Disease Model Mice
Nagata, K., Hashimoto, S., Joho, D., Fujioka, R., Matsuba, Y., Sekiguchi, M., Mihira, N., Motooka, D., Liu, Y., Okuzaki, D., et al. (2024) · eNeuro · doi:10.1523/eneuro.0260-24.2024 · Cited by 11
Datta, D., & Arnsten, A. F. T. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14477 · Cited by 11
Neuropsychiatric symptoms and apolipoprotein E genotypes in neurocognitive disorders
Lozupone, M., Leccisotti, I., Mollica, A., Berardino, G., Moretti, M. C., Altamura, M., Bellomo, A., Daniele, A., Dibello, V., Solfrizzi, V., et al. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-01274 · Cited by 11
Accelerated midlife endocrine and bioenergetic brain aging in APOE4 females
Wang, T., Mao, Z., Shang, Y., Merlini, S., Vitali, F., Wiegand, J. L., & Brinton, R. D. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1632877 · Cited by 12
Singhaarachchi, P. H., Antal, P., Calon, F., Culmsee, C., Delpech, J.-C., Feldotto, M., Geertsema, J., Hoeksema, E. E., Kőrösi, A., Layé, S., et al. (2025) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2025.102821 · Cited by 13
Nussbaumer, J., Barve, A., Zufferey, V., Espourteille, J., Kirabali, T., Konietzko, U., Razansky, D., Rominger, A., Nordberg, A. K., Buée, L., et al. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00508-2 · Cited by 11
Hong, Y. J., Kim, C. M., Lee, J. H., & Sepulcre, J. (2022) · Scientific Reports · doi:10.1038/s41598-022-18325-2 · Cited by 12
Simões, J. L. B., Sobierai, L. D., Leal, I. F., dos Santos, M. V. R., Coiado, J. V., & Bagatini, M. D. (2022) · Neuroscience · doi:10.1016/j.neuroscience.2022.12.007 · Cited by 11
Warpechowski, M., Warpechowski, J. J., Kulczyńska‐Przybik, A., & Mroczko, B. (2022) · Medical Science Monitor · doi:10.12659/msm.938826 · Cited by 11
Emmerson, J. T., Carmo, S. D., Liu, Y., Shalhoub, A., Ai, L., Bonomo, Q., Malcolm, J. C., Breuillaud, L., & Cuello, A. C. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106227 · Cited by 11
Groechel, R. C., Tripodis, Y., Alosco, M. L., Mez, J., Qiu, W. Q., Goldstein, L. E., Budson, A. E., Kowall, N. W., Shaw, L. M. J., Weiner, M. W., et al. (2023) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2023.07.021 · Cited by 12
Apolipoprotein E isoform does not influence trans-synaptic spread of tau pathology in a mouse model
Davies, C., Tulloch, J., Yip, E., Currie, L., Colom‐Cadena, M., Wegmann, S., Hyman, B. T., Wilkins, L., Hooley, M., Tzioras, M., et al. (2023) · Brain and Neuroscience Advances · doi:10.1177/23982128231191046 · Cited by 11
Contextualizing the Role of Osteopontin in the Inflammatory Responses of Alzheimer’s Disease
Lalwani, R. C., Volmar, C., Wahlestedt, C., Webster, K. A., & Shehadeh, L. A. (2023) · Biomedicines · doi:10.3390/biomedicines11123232 · Cited by 13
Integrated Genomic Analysis Revealed Associated Genes for Alzheimer’s Disease in APOE4 Non-Carriers
Jiang, S., Zhang, C., Tang, L., Zhao, L., Chen, H., & Qiu, Y. L. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190823124724 · Cited by 11
Self-citationHays, C. C., Zlatar, Z. Z., Meloy, M. J., Osuna, J., Liu, T. T., Galasko, D. R., & Wierenga, C. E. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190504 · Cited by 12
Shoubridge, A. P., Carpenter, L., Flynn, E. F., Papanicolas, L. E., Collins, J., Gordon, D., Lynn, D. J., Whitehead, C., Leong, L. E. X., Cations, M., et al. (2025) · The Journals of Gerontology Series A · doi:10.1093/gerona/glaf053 · Cited by 10
Research Progress of Lipid Metabolism-Mediated Neuroinflammation in Alzheimer’s Disease
Shen, Y., Wang, X., Liu, X., Wang, G., Hou, X., & Zhou, X. (2025) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-025-01648-9 · Cited by 12
Metabolic and inflammatory roles of glial cells in neurodegenerative and cerebrovascular diseases
OGUNLEYE, F. A., Zhou, Y., Yan, L., Abhulimen, P. O., Xu, Y., Lai, M. K. P., Okunowo, W. O., Sethi, G., Fang, C., & Ma, Y. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103120 · Cited by 11
Recent advances in Alzheimer’s disease: From molecular mechanisms to therapeutic strategies
Rudman, M. D., Ulrich, J. D., & Holtzman, D. M. (2026) · Cell · doi:10.1016/j.cell.2026.06.006 · Cited by 12
Self-citationTau polygenic risk scoring: a cost-effective aid for prognostic counseling in Alzheimer’s disease
Ramanan, V. K., Heckman, M. G., Lesnick, T. G., Przybelski, S. A., Cahn, E. J., Kosel, M., Murray, M. E., Mielke, M. M., Botha, H., Graff‐Radford, J., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02419-2 · Cited by 10
Building in vitro models of the brain to understand the role ofAPOEin Alzheimer’s disease
Pinals, R. L., & Tsai, L. (2022) · Life Science Alliance · doi:10.26508/lsa.202201542 · Cited by 10
ZCCHC17 Modulates Neuronal RNA Splicing and Supports Cognitive Resilience in Alzheimer's Disease
Bartosch, A. M. W., Youth, E. H. H., Hansen, S., Wu, Y., Buchanan, H. M., Kaufman, M. E., Xiao, H., Koo, S. Y., Ashok, A., Sivakumar, S., et al. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.2324-22.2023 · Cited by 10
The role of Apolipoprotein E4 on cognitive impairment in Parkinson’s disease and Parkinsonisms
Rosal, A. E., Martin, S. L., & Strafella, A. P. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1515374 · Cited by 10
Diaz, J. R., Martá-Ariza, M., Khodadadi‐Jamayran, A., Heguy, A., Tsirigos, A., Pankiewicz, J. E., Sullivan, P. M., & Sadowski, M. J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.845291 · Cited by 11
Self-citationWang, K., & Zhang, W. (2021) · Synapse · doi:10.1002/syn.22196 · Cited by 11
Self-citationDysregulation of neuroproteasomes by ApoE isoforms drives endogenous Tau aggregationPreprint
Paradise, V., Sabu, M., Bafia, J., Sharif, N., Nguyen, C., Konrad-Vicario, K., Mukim, R. D., Wang, X., Corjuc, B., Fu, J. M., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.29.518293 · Cited by 10
Self-citationGut microbes modulate neurodegeneration
Jain, T., & Li, Y. (2023) · Science · doi:10.1126/science.adf9548 · Cited by 10
Diverse influences on tau aggregation and implications for disease progressionPreprint
Alstyne, M. V., Pratt, J., & Parker, R. (2025) · Genes & Development · doi:10.1101/gad.352551.124 · Cited by 11
Slc9a6 mutation causes Purkinje cell loss and ataxia in the shaker rat
Figueroa, K. P., Anderson, C. J., Paul, S., Dansithong, W., Gandelman, M., Scoles, D. R., & Pulst, S. M. (2023) · Human Molecular Genetics · doi:10.1093/hmg/ddad004 · Cited by 9
Self-citationChen, X. R., Shao, Y., Sadowski, M. J., & Initiative, O. B. O. T. A. D. N. (2023) · Genes · doi:10.3390/genes14040917 · Cited by 9
MSUT2 regulates tau spreading via adenosinergic signaling mediated ASAP1 pathway in neurons
Xu, H. W., Qiu, Q., Hu, P., Hoxha, K., Jang, E., O’Reilly, M., Kim, C., He, Z., Marotta, N. P., Changolkar, L. N., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02703-3 · Cited by 10
Jabeen, K., Rehman, K., Akash, M. S. H., Hussain, A., Shahid, M., & Sadaf, B. (2024) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.70007 · Cited by 9
Targeting mitochondrial dysfunction in Alzheimer's disease: New findings and perspectives
Hroudová, J., & Fišar, Z. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111491 · Cited by 9
Alzheimer's disease: from molecular pathways to therapies
Feng, J.-Q., Yang, L.-L., Ya-xi, L., & Yao, X. (2026) · Molecular Biomedicine · doi:10.1186/s43556-026-00443-2 · Cited by 10
Liu, H., Hu, C., Liu, H., Gong, Z., Jiang, S., Xie, J., Li, Y., Liu, C., Wang, Y., Zou, C., et al. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03815-1 · Cited by 9
Tsamou, M., Pistollato, F., & Roggen, E. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201418 · Cited by 9
Alzheimers Disease-Like Neuropathology Following Exposure to Ambient Noise
Ehsanifar, M., Montazeri, Z., & Rafati, M. (2021) · Journal of Biomedical Research & Environmental Sciences · doi:10.37871/jbres1364 · Cited by 9
Santamaría‐García, H. A., Ogonowski, N. S., Báez, S., Palacio, N., Reyes, P. A., Schulte, M., López, A., Matallana, D., & Ibáñez, A. M. (2022) · BMC Neurology · doi:10.1186/s12883-022-02954-1 · Cited by 17
Weigand, A. J., Ortiz, G., Walker, K. S., Galasko, D. R., Bondi, M. W., & Thomas, K. R. (2023) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.10.016 · Cited by 10
Li, C., Lu, P., Zhang, L., He, Y., Zhang, L., Yang, L., Zhang, F., Kong, X., Tao, Q., Zhou, J., et al. (2023) · Neuroscience · doi:10.1016/j.neuroscience.2023.05.020 · Cited by 9
Early Chronic Stress Induced Changes within the Locus Coeruleus in Sporadic Alzheimer’s Disease
Minné, D., Marnewick, J. L., & Engel-Hills, P. C. (2023) · Current Alzheimer Research · doi:10.2174/1567205020666230811092956 · Cited by 10
Yazdi, M. K., Alavi, M. S., & Roohbakhsh, A. (2024) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13981 · Cited by 11
Novel Development and Prospects in Pathogenesis, Diagnosis, and Therapy of Alzheimer’s Disease
Teng, Z. (2024) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-230130 · Cited by 10
Smart polymers driven by multiple and tunable hydrogen bonds for intact phosphoprotein enrichment
Zhang, X., Lu, Q., Chen, C., Li, X., Qing, G., Sun, T., & Liang, X. (2019) · Science and Technology of Advanced Materials · doi:10.1080/14686996.2019.1643259 · Cited by 9
Argentati, C., Tortorella, I., Bazzucchi, M., Emiliani, C., Morena, F., & Martino, S. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10030115 · Cited by 10
Patient-derived iPSCs, a reliable in vitro model for the investigation of Alzheimer’s disease
Asiamah, E. A., Guo, R., Kong, D., Feng, B., He, J., Zhang, W., Liu, X., Du, X., Ma, Z., Liu, B., et al. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0065 · Cited by 9
Werhane, M. L., Thomas, K. R., Edmonds, E. C., Bangen, K. J., Tran, M., Clark, A. L., Nation, D. A., Gilbert, P. E., Bondi, M. W., Delano‐Wood, L., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170918 · Cited by 9
Self-citationLi, Y., Kang, M., Sheng, C., Chen, G., Li, T., Wang, J., Cai, Y., Wang, R., & Han, Y. (2020) · Neural Plasticity · doi:10.1155/2020/9742138 · Cited by 9
Ding, H., An, N., Au, R., Devine, S., Auerbach, S. H., Massaro, J. M., Joshi, P. S., Liu, X., Liu, Y., Mahon, E., et al. (2020) · Journal of Medical Internet Research · doi:10.2196/15376 · Cited by 9
Asiamah, E. A., Feng, B., Guo, R., Yaxing, X., Du, X., Liu, X., Zhang, J., Cui, H., & Ma, J. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-230658 · Cited by 8
Distinct factors drive the progression of tau pathology in Alzheimer’s disease
Luo, Y., Yu, H., & Ye, K. (2025) · Fundamental Research · doi:10.1016/j.fmre.2025.04.001 · Cited by 9
Navigating the treatment landscape of Alzheimer's disease: Current strategies and future directions
Mohapatra, T. K., Nayak, R. R., Ganeshpurkar, A., Tiwari, P. K., & Kumar, D. (2025) · Ibrain · doi:10.1002/ibra.12197 · Cited by 8
Fowler, C. G., Tarantino, M. I., Gillett, A. E., Muñiz, V., Anderson, M. A., Bonner, R. L., & Vichaya, E. G. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.05.010 · Cited by 8
Solders, S. K., Shen, Q., & Reas, E. T. (2025) · NeuroImage Clinical · doi:10.1016/j.nicl.2025.103805 · Cited by 8
Metadata
- Authors
- Initiative, A. D. N., Shi, Y., Yamada, K., Liddelow, S. A., Smith, S. T., Zhao, L., Luo, W., Tsai, R. M., Spina, S., Grinberg, L. T., Rojas, J. C., Gallardo, G., Wang, K., Roh, J., Robinson, G., Finn, M. B., Jiang, H., Sullivan, P. M., Baufeld, C., Wood, M. W., Sutphen, C., McCue, L., Xiong, C., Del-Aguila, J. L., Morris, J. C., Cruchaga, C., Fagan, A. M., Miller, B. L., Boxer, A. L., Seeley, W. W., Butovsky, O., Barres, B. A., Paul, S. M., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Stanford Medicine (US)
- Brigham and Women's Hospital (US)
- Cornell University (US)
- University of California, San Francisco (US)
- Voyager Therapeutics (United States) (US)
- Corresponding author
- Holtzman, David M.
- ORCID
- Shi, Yang
- Yamada, Kaoru
- Liddelow, Shane Antony
- Zhao, Lingzhi
- Luo, Wenjie
- Tsai, Richard M.
- Spina, Salvatore
- Grinberg, Lea T.
- Rojas, Julio C.
- Gallardo, Gilbert
- Roh, Joseph
- Finn, Mary Beth
- Sullivan, Patrick M.
- Wood, Michael W.
- Sutphen, Courtney
- McCue, Lena
- Xiong, Chengjie
- Morris, John C.
- Cruchaga, Carlos
- Miller, Bruce L.
- Boxer, Adam L.
- Seeley, William W.
- Butovsky, Oleg
- Barres, Ben A.
- Paul, Steven M.
- Holtzman, David M.
- Venue
- Nature
- Published
- 2017-09
- Volume
- 549
- Issue
- 7673
- Pages
- 523-527
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5641217
- OpenAlex
- W2756959977
- Cited by
- 1,220
- References
- 29
- Citations by year
- 2026: 105 · 2025: 147 · 2024: 134 · 2023: 156 · 2022: 141 · 2021: 156 · 2020: 149 · 2019: 126 · 2018: 90 · 2017: 12
- FWCI
- 76.46
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
- Funders
- U.S. Department of Defense (U01 AG024904, AG024904)
- Eli Lilly and Company (U01 AG024904, AG024904, W81XWH-12-2-0012)
- AstraZeneca
- GlaxoSmithKline
- Alzheimer's Disease Neuroimaging Initiative (W81XWH-12-2–0012, U01AG024904, AG024904, W81XWH-12-2-)
- Cure Alzheimer's Fund
- Multiple Sclerosis Society (5092A1)
- National Institutes of Health (5u01ag024904-10, W81XWH-12-2-0012, AG023501, U01-AG024904, AG019724, AG05681, NS090934, AG024904, AG 03991, AG026276)
- Genentech (W81XWH-12-2-0012, AG024904, U01 AG024904)
- National Institute on Aging (U01-AG-024904, K08AG052648, K23AG055688, R01AG051812, P50AG005681, P01AG003991, RF1AG047644, R01AG038791, R01AG054672, P01AG019724, U19AG024904, P01AG026276, P50AG023501)
- National Institute of Neurological Disorders and Stroke (K01NS096719, U54NS092089, R01NS090934, R01NS088137, RF1NS090934)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- APOE ε4, tauopathy, P301S tau transgenic mice, neuroinflammation, apolipoprotein E deficiency, TNF-α, neuronal viability, tau phosphorylation, brain atrophy, gain-of-function
- MeSH terms
- Alleles, Animals, Cell Survival, Disease Models, Animal, Genotype, Humans, Immunity, Innate, Inflammation, Mice, Transgenic, Neurons, Phosphoproteins, Phosphorylation, Tumor Necrosis Factor-alpha, tau Proteins, Microglia, Mice, Knockout, Disease Progression, Coculture Techniques, Tauopathies, Mice, Apolipoprotein E4, Gene Knock-In Techniques
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
