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This study investigated the association between severe atherosclerosis and hippocampal changes in aged human brains, focusing on blood<jats:bold>\u2013<\/jats:bold>brain barrier (BBB) dysfunction and its potential role in amyloid<jats:bold>-<\/jats:bold>beta (A\u03b2) 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.<\/jats:p>","DOI":"10.1371\/journal.pone.0324652","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T17:48:22Z","timestamp":1749664102000},"page":"e0324652","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Atherosclerosis is associated with amyloid and tau pathology via blood\u2013brain barrier dysfunction in the hippocampus of aged human 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