ArticleImmunity2025
The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway.
Article in Immunity, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Distinct factors drive the progression of tau pathology in Alzheimer's disease.Fundamental research · 2026Review
- Alzheimer disease protection from the periphery.Nature reviews. Neurology · 2026Article
- Depletion of microglial compensation in glial network: Disease-associated response dynamics in the revised amyloid hypothesis.Neuroprotection (Chichester, England) · 2026Review
- Expanding roles of cGAS-STING signaling in neuroinflammation.The Journal of clinical investigation · 2026Review
- Multiscale Approximations to Understand the Complex Role of Microglia in Alzheimer's Disease.The European journal of neuroscience · 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
- Article
- Machine learning-guided Huanglian Jiedu decoction targets STING in periodontitis-induced Alzheimer's Disease.NPJ digital medicine · 2026Article
- cGAS inhibition delays TDP-43-driven ALS Pathogenesis.bioRxiv : the preprint server for biology · 2026Article
- Inflammatory alterations mediate tau-associated neurodegeneration.Brain communications · 2026Article
- APOE3-Christchurch variant enhances neurovascular support functions of iPSC-derived mesenchymal stromal cells.Frontiers in molecular biosciences · 2026Article
- Mechanistic role of APOE lipidation in Alzheimer's disease pathogenesis.Theranostics · 2026Review
- Microglia-derived APOE2 improves remyelination even in the presence of endogenous APOE4.Journal of neuroinflammation · 2025Article
- The Christchurch point mutation in mouse APOE reduces Aβ-induced tau and α-synuclein pathologies.bioRxiv : the preprint server for biology · 2025Article
- Mitochondrial complex III-derived ROS amplify immunometabolic changes in astrocytes and promote dementia pathology.Nature metabolism · 2025Article
- From sentinels to engineers: The future of microglia in brain regeneration.Cell stem cell · 2025Article
- Identification and development of cGAS inhibitors and their uses to treat Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
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25 authors.
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Abstract
The Christchurch mutation (R136S) in the APOE3 (E3S/S) gene is associated with attenuated tau load and cognitive decline despite the presence of a causal PSEN1 mutation and high amyloid burden in the carrier. However, the molecular mechanisms enabling the E3S/S mutation to mitigate tau-induced neurodegeneration remain unclear. Here, we replaced mouse Apoe with wild-type human APOE3 or APOE3S/S on a tauopathy background. The R136S mutation decreased tau load and protected against tau-induced synaptic loss, myelin loss, and reduction in hippocampal theta and gamma power. Additionally, the R136S mutation reduced interferon responses to tau pathology in both mouse and human microglia, suppressing cGAS-STING pathway activation. Treating E3 tauopathy mice with a cGAS inhibitor protected against tau-induced synaptic loss and induced transcriptomic alterations similar to the R136S mutation across brain cell types. Thus, suppression of the microglial cGAS-STING-interferon (IFN) pathway plays a central role in mediating the protective effects of R136S against tauopathy.
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