ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Ancestral genomic functional differences in oligodendroglia: implications for Alzheimer's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed.
- Using iPSC models to examine neuron-glia interactions in neurodegenerative diseases.Bioscience reports · 2026Review
- Genetic correlation analysis of Alzheimer's disease and stroke implicates PHLPP1 as a shared locus in individuals of African ancestry.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Advances in hiPSC-Derived Brain Organoids as a Model to Study Neuroinflammation in Alzheimer's Disease.Journal of neurochemistry · 2026Review
- Disrupted lipid homeostasis as a pathogenic mechanism in ABCA7-associated Alzheimer's disease risk.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Enhanced Hi-C Capture Analysis reveals complex regulatory architecture at thebioRxiv : the preprint server for biology · 2026Article
- Local genetic correlation analysis of Alzheimer's disease and stroke implicatesmedRxiv : the preprint server for health sciences · 2025Article
- Ancestral genomic functional differences in oligodendroglia: implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Integrated genomic analysis and CRISPRi implicatesNPJ dementia · 2025Article
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Abstract
introductionThis study investigates ancestry-specific changes in induced pluripotent stem cell (iPSC)-derived oligodendroglia genomic regulation in Alzheimer's disease (AD), addressing diversity gaps by including African, Amerindian, and European ancestries in the analysis.
methodsWe generated 12 iPSC lines from AD patients and controls with different apolipoprotein E (APOE) genotypes, APOE ε3/ ε3 and APOE ε4/ ε4, across three ancestries. Lines were differentiated into neural spheroids containing oligodendrocyte lineage cells and analyzed by single-nucleus RNA sequencing, Assay for Transposase-Accessible Chromatin with sequencing (ATACseq)APO, and High-throughput Chromosome Conformation Capture (Hi-C).
resultsWe identified ancestry-specific differences in gene expression and chromatin accessibility of AD genome-wide association study candidate genes. APOE ε4/ ε4 carriers across all ancestries showed upregulated cholesterol biosynthesis genes with decreased myelination markers. iPSC-derived oligodendrocytes demonstrated high correlation (R DISCUSSION: Our findings highlight the importance of studying diverse ancestries in AD research and suggest early APOE ε4 effects on cholesterol metabolism. The validated iPSC model provides a valuable tool for investigating ancestry-specific disease mechanisms. HIGHLIGHTS: First study comparing iPSC-derived oligodendroglia across three ancestries. APOE ε4 carriers show upregulated cholesterol synthesis in oligodendroglia. Reduced myelin gene expression observed in APOE ε4/ε4 oligodendroglia. Ancestry-specific differences found in AD GWAS genes and chromatin states. Novel insights into oligodendrocyte biology relevant to Alzheimer's disease.
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