{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:53:37Z","timestamp":1793318017289,"version":"4.5.0"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"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":["RF1 AG057928"],"award-info":[{"award-number":["RF1 AG057928"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Cerebral amyloid angiopathy (CAA) is a small vessel disease characterized by amyloid \u03b2 (A\u03b2) peptide deposition within the walls of medium to small-caliber blood vessels, cerebral microhemorrhage, and blood\u2013brain barrier (BBB) leakage. It is commonly associated with late-stage Alzheimer\u2019s disease. BBB dysfunction is indicated as a pathological substrate for CAA progression with hyperpermeability, enhancing the extravasation of plasma components and inducing neuroinflammation, further worsening BBB injury and contributing to cognitive decline. Although significant effort has been made in defining the gene mutations and risk factors involved in microvascular alterations with vascular dementia and Alzheimer\u2019s disease, the intra- and intercellular pathogenic mechanisms responsible for vascular hyperpermeability are still largely unknown. The present study aimed to elucidate the transcriptional profile of the cerebral microvessels (BBB) in a murine model with CAA vasculopathy to define potential causes and underlying mechanisms of BBB injury. A comprehensive RNA sequencing analysis was performed of CAA vasculopathy in Tg-SwDI mice at 6 and 18 months in comparison to age-matched wildtype controls to examine how age and amyloid accumulation impact the transcriptional signature of the BBB. Results indicate that A\u03b2 has a critical role in triggering brain endothelial cell and BBB dysfunction in CAA vasculopathy, causing an intense proinflammatory response, impairing oxidative metabolism, altering the coagulation status of brain endothelial cells, and remodeling barrier properties. The proinflammatory response includes both adaptive and innate immunity, with pronounced induction of genes that regulate macrophage\/microglial activation and chemokines\/adhesion molecules that support T and B cell transmigration. Age has an important impact on the effects of A\u03b2, increasing the BBB injury in CAA vasculopathy. However, early inflammation, particularly microglia\/macrophage activation and the mediators of B lymphocytes\u2019 activities are underlying processes of BBB hyperpermeability and cerebral microbleeds in the early stage of CAA vasculopathy. These findings reveal a specific profile of the CAA-associated BBB injury that leads to a full progression of CAA.<\/jats:p>","DOI":"10.3389\/fncel.2022.931247","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T07:04:16Z","timestamp":1655881456000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Transcriptomic Profile of Blood\u2013Brain Barrier Remodeling in Cerebral Amyloid Angiopathy"],"prefix":"10.3389","volume":"16","author":[{"given":"Muyu","family":"Situ","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Francisco","family":"Citalan-Madrid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana M.","family":"Stamatovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard F.","family":"Keep","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuska V.","family":"Andjelkovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5967","DOI":"10.1096\/fj.202000034R","article-title":"Endothelial-derived plasma exosome proteins in Alzheimer\u2019s disease angiopathy.","volume":"34","author":"Abner","year":"2020","journal-title":"FASEB J."},{"key":"B2","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.cyto.2008.08.013","article-title":"Diagnostic utility of APOE, soluble CD40, CD40L, and Abeta1-40 levels in plasma in Alzheimer\u2019s disease.","volume":"44","author":"Ait-ghezala","year":"2008","journal-title":"Cytokine"},{"key":"B3","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.molbrainres.2005.07.014","article-title":"Genomic regulation after CD40 stimulation in microglia: relevance to Alzheimer\u2019s disease.","volume":"140","author":"Ait-Ghezala","year":"2005","journal-title":"Brain Res. 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