{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:34:59Z","timestamp":1790814899371,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03NS111486\u201001"],"award-info":[{"award-number":["R03NS111486\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>The morphological and molecular changes associated with the degeneration of arterioles in cerebral amyloid angiopathy (CAA) are incompletely understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p><jats:italic>Post mortem<\/jats:italic> brains from 26 patients with CAA or neurological controls were analyzed using light\u2010sheet microscopy, and morphological features of microvascular degeneration were quantified using surface volume rendering. Vascular stiffness was analyzed using atomic force microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULT<\/jats:title><jats:p>Vascular smooth muscle cells (VSMCs) volume was reduced by \u2248 55% in CAA. This loss of VSMC volume correlated with increased arteriolar diameter, variability in diameter, and the volume of amyloid beta (A\u03b2) deposition in the vessel. Vessels with CAA were &gt; 300% stiffer than controls. The volume of extracellular matrix cross\u2010linking enzyme lysyl oxidase (LOX) correlated closely with vascular degenerative features.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Our findings provide valuable insights into the connections among LOX, A\u03b2 deposition, and vascular stiffness in CAA. Restoration of physiologic extracellular matrix properties in penetrating arteries may yield a novel therapeutic strategy for CAA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>We conducted 3D microscopy on human brains with cerebral amyloid angiopathy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We quantified features of vascular degeneration, \u03b2\u2010amyloid, and lysyl oxidase in CAA<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Vascular degeneration correlated with A\u03b2, loss of VSMCs , and increased LOX.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Arterioles with CAA were stiffer than controls in data from atomic force microscopy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Vascular extracellular matrix properties may be a therapeutic target for CAA.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70254","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T11:11:14Z","timestamp":1749726674000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Arteriolar degeneration and stiffness in cerebral amyloid angiopathy are linked to A\u03b2 deposition and lysyl oxidase"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5508-0990","authenticated-orcid":false,"given":"Lissa","family":"Ventura\u2010Antunes","sequence":"first","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Nackenoff","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilber","family":"Romero\u2010Fernandez","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison M.","family":"Bosworth","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Prusky","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmeline","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Carvajal\u2010Tapia","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Shostak","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Harmsen","sequence":"additional","affiliation":[{"name":"Department of Pathology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bret","family":"Mobley","sequence":"additional","affiliation":[{"name":"Department of Pathology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Maldonado","sequence":"additional","affiliation":[{"name":"Vanderbilt Neurovisualization Lab Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neely","family":"Womble","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Solopova","sequence":"additional","affiliation":[{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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