{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:15:39Z","timestamp":1791918939641,"version":"4.3.4"},"reference-count":71,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Deficiency in the aquaporin\u20104 (AQP4) water channel has been linked to impaired amyloid beta (A\u03b2) clearance. However, a detailed morphopathological analysis of amyloid deposition following AQP4 therapeutic modulation remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Two\u2010month\u2010old amyloid precursor protein presenilin 1 (APPPS1) mice were treated daily for 28 days with either the AQP4 facilitator N\u2010(3\u2010(Benzyloxy)pyridin\u20102\u2010yl) benzene\u2010sulfonamide (TGN\u2010073) or the AQP4 inhibitor N\u2010(1,3,4\u2010thiadiazol\u20102\u2010yl)pyridine\u20103\u2010carboxamide dihydrochloride (TGN\u2010020) (both at 200\u00a0mg\/kg). Controls included vehicle\u2010treated APPPS1 and WT C57BL\/6J mice. Comprehensive histopathological, biochemical, and behavioral analyses were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Mice treated with AQP4 facilitator showed a significant reduction in total A\u03b2, fibrillar deposits, and soluble A\u03b2, while the AQP4 inhibitor caused a substantial increase in brain A\u03b2. AQP4\u2010facilitator treatment also reduced A\u03b240 levels and A\u03b240\/A\u03b242 ratio, whereas the inhibitor treatment increased both A\u03b240 and A\u03b242. Additionally, facilitator\u2010treated mice demonstrated reduced anxiety and improved memory performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings suggest that AQP4 modulation is a promising strategy to enhance A\u03b2 clearance\u00a0and a potential therapeutic target in Alzheimer's disease.<\/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>Intramural periarterial drainage of the interstitial fluid mediated by aquaporin\u20104 (AQP4) is a key element that ensures clearance of catabolites\/A\u03b2 peptide from within the brain parenchyma.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Inhibition of AQP4 in an APPPS1 mouse model of AD leads to increased amyloid deposition and deficient behavior compared to untreated transgenic animals.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Pharmaceutical facilitation of AQP4 in the same APPPS1 mouse model leads to a massive decrease in amyloid burden and improves the behavioral performance of the animals compared to untreated control APPPS1 mice.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70164","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T02:49:44Z","timestamp":1746586184000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Aquaporin 4 modulation drives amyloid burden and cognitive abilities in an APPPS1 mouse model of Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1782-2365","authenticated-orcid":false,"given":"Marina Daniela","family":"Manescu","sequence":"first","affiliation":[{"name":"Department of Histology University of Medicine and Pharmacy of Craiova  Craiova Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5706-8722","authenticated-orcid":false,"given":"Bogdan","family":"Catalin","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Medicine and Pharmacy of Craiova  Craiova Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4046-7310","authenticated-orcid":false,"given":"Ioana","family":"Baldea","sequence":"additional","affiliation":[{"name":"Department of Physiology Iuliu Ha\u0163ieganu University of Medicine and Pharmacy 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