{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T18:12:49Z","timestamp":1778695969421,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS094201"],"award-info":[{"award-number":["NS094201"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG053991"],"award-info":[{"award-number":["AG053991"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["733050822"],"award-info":[{"award-number":["733050822"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The accumulation of fibrillar amyloid \u03b2-protein (A\u03b2) in blood vessels of the brain, the condition known as cerebral amyloid angiopathy (CAA), is a common small vessel disease that promotes cognitive impairment and is strongly associated with Alzheimer\u2019s disease. Presently, the clinical diagnosis of this condition relies on neuroimaging markers largely associated with cerebral macro\/microbleeds. However, these are markers of late-stage disease detected after extensive cerebral vascular amyloid accumulation has become chronic. Recently, we generated a novel transgenic rat model of CAA (rTg-DI) that recapitulates multiple aspects of human CAA disease with the progressive accumulation of cerebral vascular amyloid, largely composed of A\u03b240, and the consistent emergence of subsequent microbleeds. Here, we investigated the levels of A\u03b240 in the cerebrospinal fluid (CSF) and plasma of rTg-DI rats as CAA progressed from inception to late stage disease. The levels of A\u03b240 in CSF and plasma precipitously dropped at the early onset of CAA accumulation at three months of age and continued to decrease with the progression of disease. Notably, the reduction in CSF\/plasma A\u03b240 levels preceded the emergence of cerebral microbleeds, which first occurred at about six months of age, as detected by in vivo magnetic resonance imaging and histological staining of brain tissue. These findings support the concept that reduced CSF\/plasma levels of A\u03b240 could serve as a biomarker for early stage CAA disease prior to the onset of cerebral microbleeds for future therapeutic intervention.<\/jats:p>","DOI":"10.3390\/ijms21010303","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T04:43:03Z","timestamp":1578026583000},"page":"303","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Reduced Levels of Cerebrospinal Fluid\/Plasma A\u03b240 as an Early Biomarker for Cerebral Amyloid Angiopathy in RTg-DI Rats"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2704-4938","authenticated-orcid":false,"given":"Xiaoyue","family":"Zhu","sequence":"first","affiliation":[{"name":"George &amp; Anne Ryan Institute for Neuroscience, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Xu","sequence":"additional","affiliation":[{"name":"George &amp; Anne Ryan Institute for Neuroscience, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Hoos","sequence":"additional","affiliation":[{"name":"George &amp; Anne Ryan Institute for Neuroscience, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA"},{"name":"Enzo Life Sciences, 10 Executive Blvd, Farmingdale, NY 11735, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hedok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Yale University, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helene","family":"Benveniste","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Yale University, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0660-2825","authenticated-orcid":false,"given":"William E.","family":"Van Nostrand","sequence":"additional","affiliation":[{"name":"George &amp; Anne Ryan Institute for Neuroscience, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.brainresrev.2003.08.001","article-title":"Pathogenesis of cerebral amyloid angiopathy","volume":"43","author":"Rensink","year":"2003","journal-title":"Brain Res. 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