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The mechanisms underlying CAA\u2010related vascular pathology remain unclear. Increasing evidence indicates fibrinogen, the main component in blood clots, interacts with A\u03b2 and exacerbates inflammation and co\u2010deposits in PVS of CAA\u2010positive vessels, yet its role in cerebrovascular dysfunction remains poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Using TgSwDI transgenic mice, which develop robust CAA, we examined fibrin(ogen) deposition, aquaporin\u20104 (AQP4) polarization, and caveolin\u20101 (Cav\u20101) expression. We further assessed the effects of fibrinogen depletion via small interfering RNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>TgSwDI mice showed increased fibrin(ogen) extravasation, colocalization with A\u03b2 in PVS, AQP4 depolarization, and elevated Cav\u20101 expression. Fibrinogen depletion reduced CAA, restored AQP4 polarization, decreased Cav\u20101 levels, attenuated microglial activation, and improved spatial memory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings suggest that modulating fibrinogen\u2010related pathways could be a promising strategy for mitigating CAA pathology and its associated cerebrovascular pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Fibrin(ogen)\u2010A\u03b2 colocalization aggravates CAA.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>AQP4 depolarization links fibrinogen\u2010A\u03b2 deposits to impaired clearance in CAA.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Cav\u20101 increase drives fibrinogen leakage and neuroinflammation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Fibrinogen depletion reduces CAA, restores AQP4 polarity, and improves memory.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71030","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T05:30:07Z","timestamp":1768800607000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Aquaporin\u20104 and caveolin\u20101 as mediators of fibrinogen\u2010driven cerebrovascular pathology in cerebral amyloid angiopathy"],"prefix":"10.1002","volume":"22","author":[{"given":"Vishal","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Pharmacology Physiology and Neurosciences Rutgers\u2010New Jersey Medical School  Newark New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Rochakim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Physiology and Neurosciences Rutgers\u2010New Jersey Medical School  Newark New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ferraresso","sequence":"additional","affiliation":[{"name":"Versiti Blood Research Institute  Milwaukee Wisconsin USA"},{"name":"Michael Smith Laboratories University of British Columbia  Vancouver British Columbia Canada"},{"name":"Department of Biochemistry and Molecular Biology University of British Columbia  Vancouver British Columbia 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Smith Laboratories University of British Columbia  Vancouver British Columbia Canada"},{"name":"Department of Biochemistry and Molecular Biology University of British Columbia  Vancouver British Columbia Canada"},{"name":"Departments of Surgery Biochemistry Biomedical Engineering and Pharmacology and Toxicology Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0715-7222","authenticated-orcid":false,"given":"Hyung Jin","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Physiology and Neurosciences Rutgers\u2010New Jersey Medical School  Newark New Jersey USA"},{"name":"Brain Health Institute Rutgers University  Piscataway New Jersey 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