ArticleNeuron2025
APOE genotype determines cell-type-specific pathological landscape of 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 25 papers.
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The trial behind it
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
25 citing papers in PubMed.
- Polygenicity and APOE ε4 shape response to intervention in mild cognitive impairment.Alzheimer's research & therapy · 2025Trial
- Exercise and fluoxetine in Alzheimer's disease: Molecular mechanisms of synergistic and antagonistic effects (Review).International journal of molecular medicine · 2026Review
- PLCG2 downregulation impairs synaptic function and increases Alzheimer's disease hallmarks in neuronal cultures.Nature genetics · 2026Article
- Article
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Review
- APOE4 Drives Uniquely Dysfunctional Human Microglial States in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Article
- APOE*4 risk-modifying genes and drug targets in Alzheimer's disease through cell-type-specific genomic analyses.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A critical appraisal of the link between apolipoprotein E and Tau.Current opinion in neurology · 2026Review
- Advances in hiPSC-Derived Brain Organoids as a Model to Study Neuroinflammation in Alzheimer's Disease.Journal of neurochemistry · 2026Review
- Non-microglial downregulation ofbioRxiv : the preprint server for biology · 2026Article
- Genetic risk in Alzheimer's disease.NPJ systems biology and applications · 2026Review
- Spatially resolved molecular signatures of Lewy body dementia.Acta neuropathologica · 2026Article
- APOE genotype differentially modulates prion pathology in a mouse model.Acta neuropathologica communications · 2026Article
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
- The role of nutrition and multimodal lifestyle interventions in Alzheimer's prevention and management: a mini-review.Frontiers in nutrition · 2026Review
- Microglia-derived APOE2 improves remyelination even in the presence of endogenous APOE4.Journal of neuroinflammation · 2025Article
- Effective in vivo RNA base editing via engineered cytidine deaminase APOBECs fused with PUF proteins.Nature communications · 2025Article
- Emerging Role of Oligodendrocytes Malfunction in the Progression of Alzheimer's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
30 authors.
Funding
Abstract
The apolipoprotein E (APOE) gene is the strongest genetic risk modifier for Alzheimer's disease (AD), with the APOE4 allele increasing risk and APOE2 decreasing it compared with the common APOE3 allele. Using single-nucleus RNA sequencing of the temporal cortex from APOE2 carriers, APOE3 homozygotes, and APOE4 carriers, we found that AD-associated transcriptomic changes were highly APOE genotype dependent. Comparing AD with controls, APOE2 carriers showed upregulated synaptic and myelination-related pathways, preserving synapses and myelination at the protein level. Conversely, these pathways were downregulated in APOE3 homozygotes, resulting in reduced synaptic and myelination proteins. In APOE4 carriers, excitatory neurons displayed reduced synaptic pathways similar to APOE3, but oligodendrocytes showed upregulated myelination pathways like APOE2. However, their synaptic and myelination protein levels remained unchanged or increased. APOE4 carriers also showed increased pro-inflammatory signatures in microglia but reduced responses to amyloid-β pathology. These findings reveal APOE genotype-specific molecular alterations in AD across cell types.
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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 Socratic graph.