Researchers at Mayo Clinic performed non-targeted lipidomics on cerebral vessels isolated from 89 postmortem Alzheimer's disease brains across five APOE genotypes. They found that APOE ε4 was associated with increased phosphatidylethanolamine and decreased sphingomyelin in brain blood vessels. Amyloid-β levels in cerebrovascular tissue correlated with sphingolipid changes, including sphingomyelin and ceramide. Tau pathology correlated with PE plasmalogens and lysoglycerophospholipids via network analysis. These cerebrovascular-specific lipid signatures provide new mechanistic insights into how APOE genotype shapes vascular contributions to AD and suggest potential lipid biomarkers and therapeutic targets.
