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Cerebrovascular dysfunction can have detrimental impacts on the brain and is closely associated with cognitive impairment. Clinical studies have found that cerebrovascular dysfunction is correlated with cognitive decline in neurodegenerative diseases including Alzheimer\u2019s disease (AD) and chronic traumatic encephalopathy (CTE). However, cerebrovascular changes during the progression of neurological disorders remain to be understood. Using matched and parallel studies of cerebrovasculature and brain tissue, this study set out to determine the temporal development of cerebrovascular remodeling and neurodegenerative disease progression. We examined changes to human anterior cerebral arteries (ACAs) from subjects with various degrees of AD and CTE neuropathology. Using biaxial inflation-extension testing, histological staining, and multiphoton imaging, we examined changes to the mechanical response and to the ACA wall structure. We found circumferential stiffening of the ACA with age. Furthermore, a minor relationship was reported between ACA stiffening and elevated levels of tau-based neuropathologies including neurofibrillary tangles, characteristic of both AD and CTE. Histological and multiphoton structural studies of the ACAs revealed smooth muscle cell atrophy at the media-adventitia interface and disorganization and straightening of adventitial collagen with age and disease. Our study reveals changes to the extracellular and cellular components of cerebral arteries that help describe the functional alterations of cerebrovasculature. Results from this study shed light on the complex relationship between cerebrovascular remodeling and neurodegenerative disease progression.<\/jats:p>","DOI":"10.3389\/fbioe.2025.1597917","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T07:59:49Z","timestamp":1756886389000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Cerebrovascular remodeling in aging and neurodegenerative disease progression"],"prefix":"10.3389","volume":"13","author":[{"given":"Samuel C.","family":"Halvorsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Gkousioudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Nicks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor E.","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irving J.","family":"Bigio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Zaia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thor D.","family":"Stein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s00401-020-02197-9","article-title":"Characterizing tau deposition in chronic traumatic encephalopathy (CTE): utility of the McKee CTE staging scheme","volume":"140","author":"Alosco","year":"2020","journal-title":"Acta Neuropathol."},{"key":"B2","article-title":"Alzheimer\u2019s association 2024 alzheimer\u2019s disease facts and figures","year":"2024"},{"key":"B3","doi-asserted-by":"publisher","first-page":"E1289-E1298","DOI":"10.1073\/pnas.1710329115","article-title":"Tau induces blood vessel abnormalities and angiogenesis-related gene expression in P301L transgenic mice and human Alzheimer\u2019s disease","volume":"115","author":"Bennett","year":"2018","journal-title":"Proc. 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