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.
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Early p-Tau staining types 1 and 2 were enriched in PS19-E3 mice.
“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]
The paper’s discussion of p-tau staining patterns (section labeled Abstract; page unavailable) says types 1 and 2 were enriched in TEKO mice, not TE3 mice, and type 4 was enriched in TE4 mice. It describes these patterns in 9-month-old mice; it does not identify types 1 and 2 as early-age staining. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredAPOE4 reduces the phagocytosis ability of glial cells, enhances microglia proinflammatory activation by Aβ plaques or tau aggregates, and promotes neurodegeneration in mouse models.
“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]
The paper’s Abstract reports greater microglial proinflammatory activation and neurodegeneration in ApoE4 mice with P301S tau pathology. It does not establish reduced glial phagocytosis or show that Aβ plaques trigger the reported activation; its cultured-microglia stimulation experiment used LPS. The paper also treats a direct inflammatory effect of particular tau patterns as a possibility, not a demonstrated response to tau aggregates. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPrevious studies demonstrated that deletion of Apoe and overexpression of Ldlr can reduce tau-associated neurodegeneration.
“previous studies have demonstrated that deletion of Apoe and overexpression of Ldlr can reduce tau‐associated neurodegeneration.”
From Deletion of neuronal <i>Idol</i> ameliorates Alzheimer's disease–related pathologies via APOE receptors (2025) · cites this paper as [75]
The paper’s concluding discussion (listed under Abstract in our copy; no page given) says that absence of ApoE was strongly neuroprotective in the context of tau pathology. The passages do not report that Ldlr overexpression reduces tau-associated neurodegeneration; a search for LDLR found no relevant passage. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn previous studies, brain regions of P301S: APOE4-KI mice demonstrate marked neurodegeneration compared to P301S: APOE3-KI mice at 9.5 months of age.
“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]
The paper reports significantly more brain atrophy in P301S/E4 than P301S/E3 mice, particularly in the hippocampus, piriform/entorhinal cortex, and amygdala. The reported comparison is at 9 months, not the claimed 9.5 months (main text, page unavailable). (LLM, conf=0.88)
Experimental — accuracy not yet measuredSample sizes were justified by prior publications using APP/PS1 and P301S mouse models that provided estimates of expected effect sizes and variance.
“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
The Methods > Animals passage says sample sizes were chosen using estimates to provide 80% power to detect differences of 20% or greater. It does not say those estimates came from prior APP/PS1 or P301S publications, or specify estimates of variance. No page number is available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
ApoE independently influences several key factors that drive pathogenesis of Alzheimer's disease, including β-amyloidosis, tauopathy, and synaptic dysfunction.
“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]
The paper’s Abstract says ApoE influences Aβ deposition and reports that ApoE affects tau pathogenesis independently of Aβ pathology. It also reports neuronal injury and reduced neurite arborization, but the passages do not establish an independent effect on synaptic dysfunction; that part of the cited sentence is unsupported by this source. (LLM, conf=0.85)
Experimental — accuracy not yet measuredReducing ApoE levels is generally protective in AD models.
“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]
The paper’s Abstract reports that the absence of ApoE was strongly neuroprotective in a P301S mouse model of tauopathy. That supports protection from eliminating ApoE in this model, but not the broader claim that reducing ApoE levels is generally protective across AD models. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAPOE4 exacerbates AD-related pathologies, including amyloid-beta plaques, Tau tangles, neurodegeneration and neuroinflammation.
“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]
The paper’s Abstract reports greater Aβ pathology with ApoE4 and, in P301S tau mice, higher tau levels, markedly greater brain atrophy, and more neuroinflammation. It does not establish that ApoE4 increases Tau tangles specifically; it reports tau redistribution and distinct phosphorylated-tau staining patterns instead. The mouse findings are also not direct evidence for every listed pathology in human AD. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPS19-E4 mice displayed roughly two-fold higher AT8+ p-Tau coverage area in the hippocampus than PS19-E3 mice.
“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]
The paper’s main text (Fig. 2b discussion; page unavailable in our copy) reports greater AT8-positive p-tau covered area in the hippocampus of 3-month-old TE4 mice. Extended Data Figure 4 also quantifies AT8-covered area for TE3 and TE4 mice, but the text in our copy does not give values establishing the claimed roughly two-fold difference. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn 10-month-old PS19-E4 mice, AT8 percent coverage area was negatively correlated with hippocampal volume.
“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]
The paper reports that p-tau staining patterns in 9-month-old tau/ApoE mice correlated with brain atrophy (Abstract; page not specified). It does not report the claimed negative correlation between AT8 percent coverage and hippocampal volume specifically in 10-month-old PS19-E4 mice. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPS19-E4 mice exhibited significantly reduced hippocampal volume compared to WT and PS19-E3 mice.
“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]
The Abstract reports significantly greater atrophy in 9-month-old P301S/E4 mice than in P301S/E3 mice and identifies the hippocampus as a primary site. However, Methods > Animals explicitly says the authors did not perform statistical comparisons between WT and the other mice, so the claimed significant difference from WT is not supported. (LLM, conf=0.90)
Experimental — accuracy not yet measuredAPOE2 or Apoe KO protects against, and APOE4 exacerbates, tauopathy-induced neurodegeneration.
“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]
The paper reports that ApoE4 worsens tau-mediated neurodegeneration and ApoE knockout is protective. Its Extended Data Figure 9 places E2 at approximately the same level of neurodegeneration as E3, well above knockout; the Abstract also reports neuronal damage with recombinant E2. Thus the claim overstates the evidence that E2 itself is protective, although E2 fares better than E4. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe interpretation that residue position and its impact on intermolecular interactions are critical is consistent with prior human genetics, 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 and receptor-dependent Traffick
“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 <i>APOE</i> Missense Variants R189C and W276C With Risk of Alzheimer Disease (2026) · cites this paper as [15]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIn a tauopathy mouse model (PS19, overexpressing the MAPT P301S mutation) crossed with APOE-targeted replacement mice, 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 lowest.
“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]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredAPOE is a lipid transporter expressed on astrocytes and microglia and affects numerous microglial functions including neuroinflammation and phagocytosis.
“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 <i>APOE3</i> - <i>R136S</i> mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition (2024) · cites this paper as [10]
The paper’s Abstract reports that ApoE4 increases inflammatory reactivity in cultured microglia and that ApoE genotype affects microglial activation in mice with tau pathology. The passages do not establish the claim that APOE is a lipid transporter expressed on both astrocytes and microglia, or that it affects microglial phagocytosis. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAPOE4 greatly exacerbates tau-induced neurodegeneration, partially attributed to a critical immune hub involving IFN-driven microglial activation and interaction with cytotoxic T cells.
“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 <i>APOE3</i> - <i>R136S</i> mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition (2024) · cites this paper as [60]
The paper reports that ApoE4 aggravates tau-mediated neurodegeneration and is associated with increased microglial activation (Abstract; Extended Data Figure 9). It does not identify an IFN-driven immune hub or interactions with cytotoxic T cells as the mechanism; instead, it discusses heightened innate immune reactivity and possible effects of activated microglia and astrocytes. The indexed copy provides no page numbers for these passages. (LLM, conf=0.88)
Experimental — accuracy not yet measuredApoE ablation in P301S tau transgenic mice markedly reduced brain atrophy and tau pathology compared to the presence of apoE.
“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 paper reports that ApoE knockout largely attenuated brain atrophy in P301S mice expressing human ApoE. It also reports differences in tau pathology across ApoE genotypes, but not a marked overall reduction in tau pathology with knockout: at 9 months, overall p-tau staining differences had decreased, although staining patterns differed. The reported greater neurodegeneration with ApoE4 than with ApoE2 or ApoE3 is supported (main text, passages indexed under Abstract; page unavailable). (LLM, conf=0.86)
Experimental — accuracy not yet measuredSeveral in vivo studies of E4 mice and humans show an exaggerated response to inflammation in E4 individuals.
“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
The mouse findings (section labeled Abstract; page not supplied) show greater neuroinflammation and microglial activation in ApoE4 mice with P301S tau pathology. The paper's direct test of inflammatory reactivity used cultured microglia, not an in vivo challenge, and its human findings concern disease progression rather than an inflammatory response. Thus it supports the mouse component in a specific tauopathy setting, but not the full claim as attributed to Shi et al. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAPOE4 is associated with increased amyloid-β deposition, hyperphosphorylation and aggregation of tau, and accelerated cognitive decline.
“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]
It has not been demonstrated yet that ApoE variants impact neuron loss in APP transgenic mice, but an exacerbation of the neurodegenerative phenotype has been reported in a Tau transgenic model bred on a human ApoE4 genetic background.
“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]
In a tauopathy mouse model, Apoe KO mice exhibited less tau-mediated neurodegeneration compared to those expressing APOE3 or APOE4.
“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 <i>Idol</i> ameliorates Alzheimer's disease–related pathologies via APOE receptors (2025) · cites this paper as [75]
ApoE markedly accelerates amyloid deposition and tau-mediated neurodegeneration in mouse models.
“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]
Neurodegeneration is exacerbated in a mouse model of tauopathy expressing APOE4.
“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]
Astrocytosis contributes to hippocampal degeneration in PS19-E4 mice.
“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]
Microgliosis contributes to hippocampal degeneration.
“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]
APOE4 exacerbates these phenotypes in a PS19 tauopathy model.
“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 microglial response to tauopathy appears to drive neurodegeneration.
“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]
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 mice.
“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]
ApoE4 significantly exacerbated neurodegeneration compared to apoE2 and apoE3 in P301S tau transgenic mice.
“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
APOE4 increases pTau levels and promotes tau pathology in mice.
“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
APOE4 exacerbates tau pathology in PS19 mice.
“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
APOE4 significantly alters signaling pathways associated with cholesterol homeostasis and transport.
“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]
The paper’s results discuss ApoE4-associated changes in inflammatory and normal-cell-function gene expression in tauopathy mice, but do not identify cholesterol homeostasis or transport pathways. Searches for “cholesterol homeostasis and transport,” “cholesterol,” and related lipid-pathway terms found no passage supporting the attributed claim. (LLM, conf=0.73)
Experimental — accuracy not yet measuredIn previous studies, the MGnD phenotype was similar between P301S: APOE4-KI and P301S: APOE3-KI mice.
“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]
The paper reports greater brain atrophy and neuroinflammation in P301S/E4 than P301S/E3 mice (Abstract, page unavailable), but the claim at issue is that their MGnD phenotypes were similar. A search for “MGnD” found no passage in our copy assessing or comparing that phenotype; the reported microglial gene-expression differences do not settle this specific claim. (LLM, conf=0.75)
Experimental — accuracy not yet measuredTau may play an early pathological role in Alzheimer's disease.
“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]
APOE4 drives Aβ- and tau-mediated neurodegeneration by inducing microglial and astrocytic activation.
“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]
APOE4 aggravates tau-mediated neurodegeneration in a tauopathy mouse model and induces tau aggregates in brain, while genetic ablation of APOE attenuates tau-induced neurodegeneration.
“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]
ApoE4 affects neuroinflammation, tau pathology, and tau-mediated neurodegeneration independently of Aβ pathology.
“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 PS19 tauopathy mice, ApoE4 dramatically exacerbated tau-mediated neurodegeneration.
“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
Multiple studies suggest that lowering ApoE levels reduces relevant pathology in both amyloidosis and tauopathy mouse models.
“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
Knocking out apoE protected Tau-P301S mice from neurodegeneration and neuroinflammation.
“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]
These data support apoE4's gain of toxic effects on tau pathology and its related neurodegeneration and neuroinflammation, all independent of amyloid-β.
“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 mutant human Tau-P301S transgenic mice, expression of apoE4 led to more advanced tau pathology, brain atrophy, and neuroinflammation.
“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 tau model of neurodegeneration, genetic deletion of either Apoe or Trem2 arrested neurodegeneration, demonstrating that this pathway negatively regulates the homeostatic signature.
“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]
TREM2 and ApoE signalling are linked to worsened neuroinflammation and tauopathy.
“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]
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 disease.
“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]
Genetic ablation of ApoE in various neurodegenerative mouse models shows a similar protective effect against neurodegeneration and disease severity.
“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 a tauopathy mouse model, genetic ablation of ApoE markedly reduces activation of microglia and astrocytes and ameliorates brain atrophy.
“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]
ApoE4 exacerbates tau pathogenesis and tau-mediated neurodegeneration relative to other ApoE isoforms independent of amyloid-β.
“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]
Under neurodegenerative or neuroinflammatory conditions, ApoE deficiency attenuates inflammation and disease severity.
“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]
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 pathology.
“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]
ApoE4 significantly exacerbates neurodegeneration whereas ApoE ablation strongly attenuates the damage compared to the presence of ApoE regardless of ApoE isoforms.
“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]
ApoE has an amyloid-β-independent role in regulating neurodegeneration and neuroinflammation in the setting of a tauopathy.
“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]
The protective effect of ApoE deficiency on neurodegeneration is in line with that of TREM2.
“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]
Inheritance of the ε4 allele of APOE is associated with increased Aβ deposition and tau pathology, constitutes the strongest genetic risk factor for sporadic Alzheimer's disease, and influences age at onset and progression.
“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
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Cites
Neurotoxic reactive astrocytes are induced by activated microglia
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Identification of a unique TGF-β–dependent molecular and functional signature in microglia
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Self-citationGenomic analysis of reactive astrogliosis
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Self-citationSynapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
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TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques
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Self-citationApolipoprotein E and Apolipoprotein E Receptors: Normal Biology and Roles in Alzheimer Disease
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APOE genotype-specific differences in the innate immune response
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Self-citationHuman<i>APOE</i>Isoform-Dependent Effects on Brain β-Amyloid Levels in PDAPP Transgenic Mice
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Self-citationβ‐amyloid burden is not associated with rates of brain atrophy
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APOε4 is associated with enhanced in vivo innate immune responses in human subjects
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Self-citationImpaired Autophagy in APOE4 Astrocytes
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Self-citationArgyrophilic grain disease differs from other tauopathies by lacking tau acetylation
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Self-citationApolipoprotein E gene and sporadic frontal lobe dementia
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Dose dependent effect of APOE ε4 on behavioral symptoms in frontal lobe dementia
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Gene-based association studies report genetic links for clinical subtypes of frontotemporal dementia
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Allele ϵ4 of Apolipoprotein E Shows a Dose Effect on Age at Onset of Pick Disease
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Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204 · see citing works
Self-citationAlzheimer Disease Genetics Consortium (ADGC), Kunkle, B. W., The European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, P. A. E. R. F. A. D. C. (., Grenier-Boley, B., Sims, R., Bis, J. C., Damotte, V., Naj, A. C., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0358-2 · Cited by 2,946 · see citing works
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Self-citationBlood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,294 · see citing works
Microglia in Alzheimer’s disease
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The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease
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Hallmarks of neurodegenerative diseases
Wilson, D. M., Cookson, M. R., Van Den Bosch, L., Zetterberg, H., Holtzman, D. M., & Dewachter, I. (2023) · Cell · doi:10.1016/j.cell.2022.12.032 · Cited by 1,789 · see citing works
Self-citationRole of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668 · see citing works
“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) Although the underlying molecular mechanism is still far from clear, some clues have been found.”
BackgroundApolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
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Normal aging induces A1-like astrocyte reactivity
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Self-citationMicrobiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
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Microglial signatures and their role in health and disease
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Self-citationAPOE and Alzheimer’s disease: Advances in genetics, pathophysiology, and therapeutic approaches
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Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
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Innate immune memory in the brain shapes neurological disease hallmarks
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Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease
Kametani, F., & Hasegawa, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00025 · Cited by 836 · see citing works
ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies
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Imaging the evolution and pathophysiology of Alzheimer disease
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Savelieff, M. G., Nam, G., Kang, J., Lee, H. J., Lee, M., & Lim, M. H. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00138 · Cited by 603 · see citing works
Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight
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Self-citationInteraction of Microglia and Astrocytes in the Neurovascular Unit
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Self-citationAmyloid-β-independent regulators of tau pathology in Alzheimer disease
van der Kant, R., Goldstein, L. S. B., & Ossenkoppele, R. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0240-3 · Cited by 580 · see citing works
A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward
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Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer’s disease
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LRP1 is a master regulator of tau uptake and spread
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Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration
Patani, R., Hardingham, G. E., & Liddelow, S. A. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00822-1 · Cited by 531 · see citing works
Self-citationA combination of ontogeny and CNS environment establishes microglial identity
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“Although the exact molecular effects of AD-associated risk variants in TREM2 are still being investigated, the most common position 47 arginine-to-histidine (R47H) variant appears to reduce binding to anionic phospholipids, including binding to apolipoproteins such as ApoE, and reduce lipid-induced TREM2 activity (9–1…”
BackgroundResultInfluentialSelf-citationTau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation
Chen, Y., & Yu, Y. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02853-3 · Cited by 516 · see citing works
The probabilistic model of Alzheimer disease: the amyloid hypothesis revised
Frisoni, G. B., Altomare, D., Thal, D. R., Ribaldi, F., van der Kant, R., Ossenkoppele, R., Blennow, K., Cummings, J., van Duijn, C., Nilsson, P. M., et al. (2022) · Nature Reviews Neuroscience · doi:10.1038/s41583-021-00533-w · Cited by 513 · see citing works
APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes
Blanchard, J. W., Akay, L. A., Davila-Velderrain, J., von Maydell, D., Mathys, H., Davidson, S. M., Effenberger, A., Chen, C.-Y., Maner-Smith, K., Hajjar, I., et al. (2022) · Nature · doi:10.1038/s41586-022-05439-w · Cited by 493 · see citing works
New insights into the role of TREM2 in Alzheimer’s disease
Gratuze, M., Leyns, C. E. G., & Holtzman, D. M. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0298-9 · Cited by 489 · see citing works
Self-citationThe Meningeal Lymphatic System: A New Player in Neurophysiology
Da Mesquita, S., Fu, Z., & Kipnis, J. (2018) · Neuron · doi:10.1016/j.neuron.2018.09.022 · Cited by 479 · see citing works
Reiman, E. M., Arboleda-Velasquez, J. F., Quiroz, Y. T., Huentelman, M. J., Beach, T. G., Caselli, R. J., Chen, Y., Su, Y., Myers, A. J., Hardy, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14279-8 · Cited by 473 · see citing works
Self-citationGamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection
Adaikkan, C., Middleton, S. J., Marco, A., Pao, P., Mathys, H., Kim, D. N.-W., Gao, F., Young, J. Z., Suk, H., Boyden, E. S., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.04.011 · Cited by 469 · see citing works
Bidirectional Microglia–Neuron Communication in Health and Disease
Szepesi, Z., Manouchehrian, O., Bachiller, S., & Deierborg, T. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00323 · Cited by 459 · see citing works
Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy
Zheng, Q., & Wang, X. (2024) · Protein & Cell · doi:10.1093/procel/pwae026 · Cited by 454 · see citing works
ApoE4: an emerging therapeutic target for Alzheimer’s disease
Safieh, M., Korczyn, A. D., & Michaelson, D. M. (2019) · BMC Medicine · doi:10.1186/s12916-019-1299-4 · Cited by 449 · see citing works
Practical considerations for choosing a mouse model of Alzheimer’s disease
Jankowsky, J. L., & Zheng, H. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0231-7 · Cited by 449 · see citing works
Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model
Shi, Y., Manis, M., Long, J., Wang, K., Sullivan, P. M., Remolina Serrano, J., Hoyle, R., & Holtzman, D. M. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20190980 · Cited by 448 · see citing works
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Tau molecular diversity contributes to clinical heterogeneity in Alzheimer’s disease
Dujardin, S., Commins, C., Lathuiliere, A., Beerepoot, P., Fernandes, A. R., Kamath, T. V., De Los Santos, M. B., Klickstein, N., Corjuc, D. L., Corjuc, B. T., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0938-9 · Cited by 438 · see citing works
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Self-citationAstrocyte contribution to dysfunction, risk and progression in neurodegenerative disorders
Brandebura, A. N., Paumier, A., Onur, T. S., & Allen, N. J. (2023) · Nature Reviews Neuroscience · doi:10.1038/s41583-022-00641-1 · Cited by 427 · see citing works
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Self-citationCholesterol and matrisome pathways dysregulated in astrocytes and microglia
TCW, J., Qian, L., Pipalia, N. H., Chao, M. J., Liang, S. A., Shi, Y., Jain, B. R., Bertelsen, S. E., Kapoor, M., Marcora, E., et al. (2022) · Cell · doi:10.1016/j.cell.2022.05.017 · Cited by 411 · see citing works
Self-citationWhat is the evidence that tau pathology spreads through prion-like propagation?
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Apolipoprotein E in lipoprotein metabolism, health and cardiovascular disease
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ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism
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Mechanisms of sex differences in Alzheimer’s disease
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The complexity of tau in Alzheimer’s disease
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Assessment of Racial Disparities in Biomarkers for Alzheimer Disease
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Self-citationMicroglia: Agents of the CNS Pro-Inflammatory Response
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TDP-43 Pathology in Alzheimer’s Disease
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APOE and Alzheimer’s Disease: From Lipid Transport to Physiopathology and Therapeutics
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Beyond the neuron–cellular interactions early in Alzheimer disease pathogenesis
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Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau
Hohman, T. J., Dumitrescu, L., Barnes, L. L., Thambisetty, M., Beecham, G., Kunkle, B., Gifford, K. A., Bush, W. S., Chibnik, L. B., Mukherjee, S., et al. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2018.0821 · Cited by 340 · see citing works
Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome
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Self-citationMicroglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy
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Self-citationSolving neurodegeneration: common mechanisms and strategies for new treatments
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Self-citationApoE Cascade Hypothesis in the pathogenesis of Alzheimer’s disease and related dementias
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Self-citationThe identity and function of microglia in neurodegeneration
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Gene therapy for neurological disorders: progress and prospects
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Apolipoprotein E: Structural Insights and Links to Alzheimer Disease Pathogenesis
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Self-citationApoE facilitates the microglial response to amyloid plaque pathology
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Self-citationEmerging roles of innate and adaptive immunity in Alzheimer’s disease
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Self-citationActivation of innate immune cGAS-STING pathway contributes to Alzheimer’s pathogenesis in 5×FAD mice
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Challenges and hopes for Alzheimer’s disease
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Novel Alzheimer risk genes determine the microglia response to amyloid-β but not to TAU pathology
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Deciphering the astrocyte reaction in Alzheimer's disease
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Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model
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The path forward in Alzheimer's disease therapeutics: Reevaluating the amyloid cascade hypothesis
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The biological pathways of Alzheimer disease: a review
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Tau: Enabler of diverse brain disorders and target of rapidly evolving therapeutic strategies
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Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
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Alzheimer’s pathogenic mechanisms and underlying sex difference
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Association of Apolipoprotein E ε4 With Medial Temporal Tau Independent of Amyloid-β
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Self-citationTFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading
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Impact of TREM2R47H variant on tau pathology–induced gliosis and neurodegeneration
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Self-citationErratum: Gene therapy for neurological disorders: progress and prospects
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Self-citation
- 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 · 2012: 1
- 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
- Health Sciences › Medicine › Physiology › 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
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