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Although IFITM3 knockout reduces amyloid \u03b2 protein (A\u03b2) production, its cell\u2010specific effect on AD remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Single nucleus RNA sequencing (snRNA\u2010seq) was used to assess IFITM3 expression. Adeno\u2010associated virus\u2010BI30 (AAV\u2010BI30) was injected to reduce IFITM3 expression in the cerebrovascular endothelial cells (CVECs). The effects on AD phenotypes in cells and AD mice were examined through behavioral tests, two\u2010photon imaging, flow cytometry, Western blot, immunohistochemistry, and quantitative polymerase chain reaction assay (qPCR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      IFITM3 expression was increased in the CVECs of patients with AD. Overexpression of\n                      <jats:italic>IFITM3<\/jats:italic>\n                      in primary endothelial cells enhanced A\u03b2 generation through regulating beta\u2010site APP cleaving enzyme 1 (BACE1) and \u03b3\u2010secretase. A\u03b2 further increased IFITM3 expression, creating a vicious cycle. Knockdown of IFITM3 in CVECs decreased A\u03b2 accumulation within cerebrovascular walls, reduced Alzheimer's\u2010related pathology, and improved cognitive performance in AD transgenic mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Knockdown of IFITM3 in CVECs alleviates AD pathology and cognitive impairment. Targeting cerebrovascular endothelial IFITM3 holds promise for AD treatment.<\/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>\n                            Interferon\u2010induced transmembrane protein 3 (\n                            <jats:italic>IFITM3<\/jats:italic>\n                            ) expression was increased in the cerebrovascular endothelial cells (CVECs) of patients with Alzheimer's Disease (AD).\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Cerebrovascular endothelial IFITM3 regulates amyloid \u03b2 protein (A\u03b2) generation through regulating beta\u2010site APP cleaving enzyme 1 (BACE1) and \u03b3\u2010secretase.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Knockdown of IFITM3 in CVECs reduces A\u03b2 deposits and improves cognitive impairments in AD transgenic mice.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Cerebrovascular endothelial IFITM3 could be a potential target for the treatment of AD.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14543","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T05:51:32Z","timestamp":1736833892000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Inhibition of IFITM3 in cerebrovascular endothelium alleviates 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