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AQP4 modulates water influx and efflux in the interstitial fluid, yet how AQP4 localization impacts cerebral amyloid angiopathy (CAA) remains poorly understood. Here we show that astrocytic end feet and AQP4 are displaced from amyloid-bearing vessels in a prion-CAA mouse model that expresses GPI-anchorless PrP\n                  <jats:sup>C<\/jats:sup>\n                  . Displacing AQP4 genetically through deleting alpha-syntrophin (\n                  <jats:italic>\n                    Snta1\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  ) led to a marked prolongation in survival, together with reduced microglial inflammation and C1q, in prion-CAA-affected mice. Additionally, synaptic structural proteins were better maintained. Finally, the level and distribution of prion aggregates were similar among the mice, indicating that prion conversion and spread was not affected. These results suggest that reducing AQP4 water channel function slows the decline in a vascular amyloid disease by reducing neuroinflammation.\n                <\/jats:p>","DOI":"10.64898\/2026.07.13.732468","type":"posted-content","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T04:30:19Z","timestamp":1784349019000},"source":"Crossref","is-referenced-by-count":0,"title":["Aquaporin-4 mislocalization from astrocyte endfeet prolongs survival in a prion-cerebral amyloid angiopathy model"],"prefix":"10.64898","author":[{"given":"Samantha","family":"Flores","sequence":"first","affiliation":[{"name":"Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Wilpitz","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ojeda-Juarez","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrett","family":"Danque","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Sumowski","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail","family":"Funk","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adela","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don","family":"Pizzo","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Richards","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J.","family":"Iliff","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina J.","family":"Sigurdson","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California at San Diego, La Jolla, CA 92093, USA"},{"name":"Department of Pathology, Immunology, and Microbiology, University of California at Davis, Davis, CA 95616, USA"},{"name":"Medicine, University of California at San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072014550671000_2026.07.13.732468v1.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6801762"},{"key":"2026072014550671000_2026.07.13.732468v1.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308413101"},{"issue":"1","key":"2026072014550671000_2026.07.13.732468v1.3","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41467-026-68374-8","article-title":"The glymphatic system clears amyloid beta and tau from brain to plasma in humans","volume":"17","year":"2026","journal-title":"Nat Commun"},{"key":"2026072014550671000_2026.07.13.732468v1.4","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa179"},{"key":"2026072014550671000_2026.07.13.732468v1.5","doi-asserted-by":"crossref","unstructured":"Yan X , Hu Y , Wang B , Wang S , Zhang X . 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