{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T09:28:20Z","timestamp":1793870900477,"version":"4.6.1"},"reference-count":183,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Aging is associated with aortic stiffening (AoSt), a condition characterized by diminished aortic elasticity that predisposes individuals to cognitive decline, including Alzheimer\u2019s disease (AD). Emerging evidence implicates medin, which is derived from milk fat globule-EGF factor 8 protein (MFG-E8), as a key link between AoSt and AD. Medin aggregates into aortic medial amyloid (AMA), which is found in approximately 97% of Caucasian individuals aged 50 and above, contributing to vascular inflammation, calcification, and loss of arterial elasticity. These changes may promote hyperpulsatile cerebral blood flow and impair glymphatic clearance, resulting in increased deposition of neurotoxic proteins, such as amyloid-\u03b2 (A\u03b2) and possibly medin, which colocalizes with vascular A\u03b2 in the brain. Medin enhances A\u03b2 aggregation, generating heterologous fibrils, and thereby contributes to cerebrovascular dysfunction and neuroinflammation. This interaction (cross-seeding) may deteriorate amyloid pathology in both the vasculature and the parenchyma in AD. Furthermore, medin per se causes endothelial dysfunction, increases oxidative stress, and activates glial cells, promoting the development of a pro-inflammatory environment that enhances cognitive decline. In this manuscript, we contend that medin might act as a bridge connecting the age-related increase in aortic stiffness to AD, and therefore, medin might present a novel therapeutic target within this context. This hypothesis deserves experimental and clinical validation.<\/jats:p>","DOI":"10.3390\/biom15081148","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T15:30:52Z","timestamp":1754667052000},"page":"1148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Aortic Stiffness and Alzheimer\u2019s Disease: The Medin Connection"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6433-4016","authenticated-orcid":false,"given":"Filippos","family":"Triposkiadis","sequence":"first","affiliation":[{"name":"European University Cyprus, 1516 Nicosia, Cyprus"},{"name":"Department of Cardiology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9439-3946","authenticated-orcid":false,"given":"Andrew","family":"Xanthopoulos","sequence":"additional","affiliation":[{"name":"European University Cyprus, 1516 Nicosia, Cyprus"},{"name":"Department of Cardiology, University Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, 41500 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harisios","family":"Boudoulas","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk L.","family":"Brutsaert","sequence":"additional","affiliation":[{"name":"Department of Medicine & Cardiology, University of Antwerp, 2000 Antwerpen, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.jcmg.2008.08.002","article-title":"Aortic dimensions and stiffness in normal adults","volume":"1","author":"Farnsworth","year":"2008","journal-title":"JACC Cardiovasc. 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