Demographics of the subjects.

Atherosclerosis, a chronic vascular condition characterized by lipid accumulation and arterial plaque formation, has emerged as a significant contributor to neurodegenerative diseases, including Alzheimer’s disease (AD). This study investigated the association between severe atherosclerosis and hippocampal changes in aged human brains, focusing on blood–brain barrier (BBB) dysfunction and its potential role in amyloid-beta (Aβ) and phosphorylated tau (pTau) pathology. Using multiplex immunohistochemical staining of postmortem brain tissue, we demonstrated that atherosclerosis-associated vascular damage leads to endothelial and smooth muscle cell apoptosis, exacerbates cerebral amyloid angiopathy (CAA), and promotes perivascular tau accumulation. These findings highlight a potential association between vascular health and neurodegeneration, offering insights into potential therapeutic targets for mitigating AD progression.