ArticleNeuron2025
ApoE3 R136S binds to Tau and blocks its propagation, suppressing neurodegeneration in mice with Alzheimer's disease.
Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Distinct factors drive the progression of tau pathology in Alzheimer's disease.Fundamental research · 2026Review
- A critical appraisal of the link between apolipoprotein E and Tau.Current opinion in neurology · 2026Review
- Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice.Translational psychiatry · 2026Article
- Apolipoprotein E4 in Alzheimer's Disease: Role in Pathology, Lipid Metabolism, and Drug Treatment.International journal of molecular sciences · 2026Review
- Mechanistic role of APOE lipidation in Alzheimer's disease pathogenesis.Theranostics · 2026Review
- The Christchurch point mutation in mouse APOE reduces Aβ-induced tau and α-synuclein pathologies.bioRxiv : the preprint server for biology · 2025Article
- β-Amyloid induces microglial expression of GPC4 and APOE leading to increased neuronal tau pathology and toxicity.Molecular neurodegeneration · 2025Article
- The Protective Mechanism of ApoE3 R136S in Alzheimer's Disease: A New Hope for Neurodegeneration.Phenomics (Cham, Switzerland) · 2025Article
- ApoE3 Christchurch and tau interaction as a protective mechanism against Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The APOE-Microglia Axis in Alzheimer's Disease: Functional Divergence and Therapeutic Perspectives-A Narrative Review.Brain sciences · 2025Review
- Protective genetic variants against Alzheimer's disease.The Lancet. Neurology · 2025Review
- Dysregulated calcium signaling in the aged primate association cortices: vulnerability to Alzheimer's disease neuropathology.Frontiers in aging neuroscience · 2025Review
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Authors and funding
8 authors.
Funding
Abstract
PSEN1 E280A carrier for the APOE3 Christchurch variant (R136S) is protected against Alzheimer's disease (AD) symptoms with a distinct anatomical pattern of Tau pathology. However, the molecular mechanism accounting for this protective effect remains incompletely understood. Here, we show that the ApoE3 R136S mutant strongly binds to Tau and reduces its uptake into neurons and microglia compared with ApoE3 wild type (WT), diminishing Tau fragmentation by asparagine endopeptidase (AEP), proinflammatory cytokines by Tau pre-formed fibrils (PFFs) or β-amyloid (Aβ), and neurotoxicity. Further, ApoE3 R136S demonstrates more robust effects in attenuating AEP activation and Tau PFF spreading in the brains of both 5xFAD and Tau P301S mice than in ApoE3 WT, leading to improved cognitive functions. Thus, our findings support the idea that ApoE3 R136S strongly binds Tau and decreases its cellular uptake, abrogating Tau pathology propagation in AD brains.
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