{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:16:11Z","timestamp":1790741771485,"version":"4.1.0"},"reference-count":85,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["1RF1AG074289-01"],"award-info":[{"award-number":["1RF1AG074289-01"]}]},{"name":"National Institutes of Health","award":["1RF1AG069039-01"],"award-info":[{"award-number":["1RF1AG069039-01"]}]},{"name":"National Institutes of Health","award":["P30AG066511"],"award-info":[{"award-number":["P30AG066511"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a debilitating neurodegenerative disease characterized by the accumulation of extracellular amyloid-\u03b2 peptides (A\u03b2) within the cerebral parenchyma and vasculature, which is known as cerebral amyloid angiopathy (CAA). This study utilized confocal imaging to investigate heparan sulfate (HS) expression within the cerebrovasculature and its associations with A\u03b2, gender, and ApoE4 genotype in AD. Our investigation revealed elevated levels of HS in the cerebrovasculature of AD patients with severe CAA. Additionally, these patients exhibited higher HS colocalization with A\u03b2 in the cerebrovasculature, including both endothelial and vascular smooth muscle cell compartments. Intriguingly, a reversal in the polarized expression of HS within the cerebrovasculature was detected in AD patients with severe CAA. Furthermore, male patients exhibited lower levels of both parenchymal and cerebrovascular HS. Additionally, ApoE4 carriers displayed heightened cerebrovascular A\u03b2 expression and a tendency of elevated cerebrovascular HS levels in AD patients with severe CAA. Overall, these findings reveal potential intricate interplay between HS, A\u03b2, ApoE, and vascular pathology in AD, thereby underscoring the potential roles of cerebrovascular HS in CAA development and AD pathology. Further study of the underlying mechanisms may present novel therapeutic avenues for AD treatment.<\/jats:p>","DOI":"10.3390\/ijms25073964","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:58:38Z","timestamp":1712105918000},"page":"3964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Vascular Heparan Sulfate and Amyloid-\u03b2 in Alzheimer\u2019s Disease Patients"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2265-5852","authenticated-orcid":false,"given":"Ilayda Ozsan","family":"McMillan","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33613, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marla","family":"Gearing","sequence":"additional","affiliation":[{"name":"Department of Pathology, Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1454-2719","authenticated-orcid":false,"given":"Lianchun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33613, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","article-title":"The neuropathological diagnosis of Alzheimer\u2019s disease","volume":"14","author":"DeTure","year":"2019","journal-title":"Mol. 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