Atherosclerosis is associated with amyloid and tau pathology via blood–brain barrier dysfunction in the hippocampus of aged human brains

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.