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Epigenetic and Genomic Risk of Alzheimer’s Disease
Alzheimer’s disease (AD) is often co-morbid with cerebral small vessel disease (SVD), and vascular brain endothelial cells (BECs) exhibit a strong expression of genes linked to AD genetic risk. However, the gene regulatory networks of neurovascular cells and their connection to genetic disease risk remain largely unstudied. We generated gene regulomes for human BECs, mural cells, and other brain cell types, revealing that AD heritability is primarily related to immune pathways, with moderate enrichment in BECs. Whereas SVD is broadly enriched across neurovascular unit, including astrocytes. Enhancer-to-gene interactions implicate amyloid-related processes in both AD and SVD, and gene prioritization and drug analysis point to hypertension medications as potential treatments for AD.
