ArticleNature neuroscience2023
The APOE-R136S mutation protects against APOE4-driven Tau pathology, neurodegeneration and neuroinflammation.
Article in Nature neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
68 citing papers in PubMed, 3 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- The role of APOE ε4 in modulating the relationship between non-genetic risk factors and dementia: a system review and meta-analysis.Journal of neurology · 2025Pooled it
- Human induced pluripotent stem cell models for Alzheimer's disease research: a bibliometric analysis.Frontiers in human neuroscience · 2025Pooled it
- Pooled it
- Review
- 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
- Protective mutations associated with APOE in Alzheimer's disease.Molecular psychiatry · 2026Review
- Frontotemporal dementia associated CHCHD10Cell death & disease · 2026Article
- The past, present, and future of Alzheimer's disease-part 3: the future.Arquivos de neuro-psiquiatria · 2026Review
- Mechanistic insights and therapeutic potential of targeting the cGAS-STING pathway in neurodegenerative diseases.Journal of neuroinflammation · 2026Review
- The Genetics of TDP-43 Type C Neurodegeneration: A Whole-Genome Sequencing Study and Literature Review.Neurology. Genetics · 2026Article
- 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
- Interactome mapping in human excitatory neurons reveals novel risk genes and pathways in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- Circ-FoxO3 alleviates APOE4-induced brain pathology through FoxO3-mediated autophagy.Molecular genetics and genomics : MGG · 2026Article
- APOE3-Christchurch variant enhances neurovascular support functions of iPSC-derived mesenchymal stromal cells.Frontiers in molecular biosciences · 2026Article
- Amyloid-Frontiers in aging neuroscience · 2026Article
- Neuronal APOE4 drives damaging lipid accumulation via contact-dependent neuron-oligodendrocyte-microglia interaction in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- Brain Region-Specific Accumulation of Amyloidosis-Associated Proteins in Postmortem Brain Tissues of Alzheimer's Disease Patients.Molecular neurobiology · 2025Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (LOAD), leading to earlier age of clinical onset and exacerbating pathologies. There is a critical need to identify protective targets. Recently, a rare APOE variant, APOE3-R136S (Christchurch), was found to protect against early-onset AD in a PSEN1-E280A carrier. In this study, we sought to determine if the R136S mutation also protects against APOE4-driven effects in LOAD. We generated tauopathy mouse and human iPSC-derived neuron models carrying human APOE4 with the homozygous or heterozygous R136S mutation. We found that the homozygous R136S mutation rescued APOE4-driven Tau pathology, neurodegeneration and neuroinflammation. The heterozygous R136S mutation partially protected against APOE4-driven neurodegeneration and neuroinflammation but not Tau pathology. Single-nucleus RNA sequencing revealed that the APOE4-R136S mutation increased disease-protective and diminished disease-associated cell populations in a gene dose-dependent manner. Thus, the APOE-R136S mutation protects against APOE4-driven AD pathologies, providing a target for therapeutic development against AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.