ArticleNature neuroscience2021
Neuronal ApoE upregulates MHC-I expression to drive selective neurodegeneration in Alzheimer's disease.
Article in Nature neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
106 citing papers in PubMed, 3 syntheses or guidelines pooled it, 188 citations in OpenAlex.
- Biomarkers in Ataxia-Telangiectasia: a Systematic Review.Journal of neurology · 2025Pooled it
- Transcriptomics Meta-Analysis Reveals Phagosome and Innate Immune System Dysfunction as Potential Mechanisms in the Cortex of Alzheimer's Disease Mouse Strains.Journal of molecular neuroscience : MN · 2023Pooled it
- Pooled it
- Review
- Long-term major histocompatibility complex class I suppression in astronauts and clinical implications.Communications biology · 2026Review
- Deciphering spatial heterogeneity by multimodal spatial transcriptomics modelling with SpatialModal.Bioinformatics (Oxford, England) · 2026Article
- Article
- Integrative multi-omics reveals MHC class II-mediated neuroinflammation and systemic metabolic dysregulation as transdiagnostic drivers in major brain disorders.Translational psychiatry · 2026Article
- Protective mutations associated with APOE in Alzheimer's disease.Molecular psychiatry · 2026Review
- Exceptional Longevity Modifying Allele APOE2 Promotes DNA Signaling Pathways Resisting Cellular Senescence in Human Neurons.Aging cell · 2026Article
- Neuronal APOE4-induced early hippocampal network hyperexcitability in Alzheimer's disease pathogenesis.Nature aging · 2026Article
- APOE4 exacerbates glucocorticoid stress hormone-induced tau pathology via mitochondrial dysfunction.Cell death & disease · 2026Article
- ApoE4 Drives Microglial Lipid Dysregulation in Alzheimer's Disease via Epigenetic Reprogramming of the Asxl1/LXRα-H3K4me3 Axis.Journal of neuroinflammation · 2026Article
- Exploring the toxic mechanism of cypermethrin-induced neurodegeneration diseases via network toxicology and molecular docking.Scientific reports · 2026Article
- ACSS2 upregulation enhances neuronal resilience to aging and tau-associated neurodegeneration.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Association between Alzheimer's disease and MHC-I antigen processing and presentation pathway: a narrative review.Frontiers in immunology · 2026Review
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
- CD8Frontiers in immunology · 2026Review
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Neuronal APOE4 drives damaging lipid accumulation via contact-dependent neuron-oligodendrocyte-microglia interaction in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
46 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Selective neurodegeneration is a critical causal factor in Alzheimer's disease (AD); however, the mechanisms that lead some neurons to perish, whereas others remain resilient, are unknown. We sought potential drivers of this selective vulnerability using single-nucleus RNA sequencing and discovered that ApoE expression level is a substantial driver of neuronal variability. Strikingly, neuronal expression of ApoE-which has a robust genetic linkage to AD-correlated strongly, on a cell-by-cell basis, with immune response pathways in neurons in the brains of wild-type mice, human ApoE knock-in mice and humans with or without AD. Elimination or over-expression of neuronal ApoE revealed a causal relationship among ApoE expression, neuronal MHC-I expression, tau pathology and neurodegeneration. Functional reduction of MHC-I ameliorated tau pathology in ApoE4-expressing primary neurons and in mouse hippocampi expressing pathological tau. These findings suggest a mechanism linking neuronal ApoE expression to MHC-I expression and, subsequently, to tau pathology and selective neurodegeneration.
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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.