Longevity & AgingBrain Vascular Multi-Omics Atlas Maps Genetic Risk for Alzheimer's and Stroke
Researchers developed MultiVINE-seq, a technique that simultaneously profiles gene expression and chromatin accessibility in human brain vascular, perivascular, and immune cells from 30 donors. By overlaying genome-wide association study (GWAS) data onto this atlas, they mapped 2,605 previously uncharacterized disease-risk variants to specific cell types and target genes. Cerebrovascular disease variants were found to disrupt extracellular matrix genes in endothelial, mural, and fibroblast cells, compromising vessel structural integrity. Alzheimer's disease variants, by contrast, dysregulate inflammatory signaling in endothelial and immune cells. A standout finding links a lead AD variant to enhanced PTK2B expression in brain CD8 T cells, implicating adaptive immunity in Alzheimer's pathogenesis.
