ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2023
Ancestry-related differences in chromatin accessibility and gene expression of APOE ε4 are associated with Alzheimer's disease risk.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Molecular programs in human locus coeruleus link APOE and neuromelanin to Alzheimer's vulnerability.Acta neuropathologica · 2026Article
- Epigenetic mechanisms in traumatic brain injury: a focus on astrocytes and therapeutic implications.Journal of neuroinflammation · 2026Review
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Enhanced Hi-C Capture Analysis reveals complex regulatory architecture at thebioRxiv : the preprint server for biology · 2026Article
- Impact of Alzheimer's disease risk factors and local neuromelanin content on the transcriptomic landscape of the human locus coeruleus.bioRxiv : the preprint server for biology · 2025Article
- Ancestral genomic functional differences in oligodendroglia: implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Chromatin accessibility provides a window into the genetic etiology of human brain disease.Trends in genetics : TIG · 2025Review
- Exploring potential mechanisms of an African protective locus for Alzheimer's disease in APOEε4 carriers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Apolipoprotein E in Alzheimer's disease: molecular insights and therapeutic opportunities.Molecular neurodegeneration · 2025Review
- Somatic and Stem Cell Bank to study the contribution of African ancestry to dementia: African iPSC Initiative.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Astrocyte epigenetics as a priority area in neuroscience research.Frontiers in molecular neuroscience · 2025Article
- Eligibility for anti-amyloid treatment in a multiethnic community-based study.Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Authors and funding
20 authors at 8 institutions in 1 country.
Funding
Abstract
introductionEuropean local ancestry (ELA) surrounding apolipoprotein E (APOE) ε4 confers higher risk for Alzheimer's disease (AD) compared to African local ancestry (ALA). We demonstrated significantly higher APOE ε4 expression in ELA versus ALA in AD brains from APOE ε4/ε4 carriers. Chromatin accessibility differences could contribute to these expression changes.
methodsWe performed single nuclei assays for transposase accessible chromatin sequencing from the frontal cortex of six ALA and six ELA AD brains, homozygous for local ancestry and APOE ε4.
resultsOur results showed an increased chromatin accessibility at the APOE ε4 promoter area in ELA versus ALA astrocytes. This increased accessibility in ELA astrocytes extended genome wide. Genes with increased accessibility in ELA in astrocytes were enriched for synapsis, cholesterol processing, and astrocyte reactivity. DISCUSSION: Our results suggest that increased chromatin accessibility of APOE ε4 in ELA astrocytes contributes to the observed elevated APOE ε4 expression, corresponding to the increased AD risk in ELA versus ALA APOE ε4/ε4 carriers.
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