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Exercise not only reduces the risk factors for AD but also confers direct protection against cognitive decline. However, the exact molecular mechanisms remain elusive, particularly whether exercise can liberate the function of the blood\u2013brain barrier. Here, we demonstrate that long\u2010term exercise promotes the clearance of brain amyloid\u2010\u03b2 by improving the function of the blood\u2013brain barrier in 5XFAD mice. Significantly, treating primary brain pericytes or endothelial cells with exosomes isolated from the brain of exercised 5XFAD mice improves cell proliferation and upregulates PDGFR\u03b2, ZO\u20101, and claudin\u20105. Moreover, exosomes isolated from exercised mice exhibit significant changes in miR\u2010532\u20105p. Administration or transfection of miR\u2010532\u20105p to sedentary mice or primary brain pericytes and endothelial cells reproduces the improvement of blood\u2013brain barrier function. Exosomal miR\u2010532\u20105p targets\n                    <jats:italic>EPHA4<\/jats:italic>\n                    , and accordingly, expression of EphA4 is decreased in exercised mice and miR\u2010532\u20105p overexpressed mice. A specific siRNA targeting\n                    <jats:italic>EPHA4<\/jats:italic>\n                    recapitulates the effects on blood\u2013brain barrier\u2010associated cells observed in exercised 5XFAD mice. Overall, our findings suggest that exosomes released by the brain contain a specific miRNA that is altered by exercise and has an impact on blood\u2013brain barrier function in AD.\n                  <\/jats:p>","DOI":"10.1111\/acel.13748","type":"journal-article","created":{"date-parts":[[2022,12,10]],"date-time":"2022-12-10T00:08:30Z","timestamp":1670630910000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Exosomal\n                    <scp>miR<\/scp>\n                    \u2010532\u20105p induced by long\u2010term exercise rescues blood\u2013brain barrier function in\n                    <scp>5XFAD<\/scp>\n                    mice via downregulation of\n                    <i>EPHA4<\/i>"],"prefix":"10.1111","volume":"22","author":[{"given":"Xiaoyan","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Neurology Shandong Provincial Hospital, Shandong University  Jinan Shandong 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Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"},{"name":"Shandong Provincial Clinical Research Center for Neurological Diseases  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7468-0083","authenticated-orcid":false,"given":"Min","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology Shandong Provincial Hospital, Shandong University  Jinan Shandong China"},{"name":"Department of Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"},{"name":"Shandong Provincial Clinical Research Center for Neurological Diseases  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurology Shandong Provincial Hospital, Shandong University  Jinan Shandong China"},{"name":"Department of Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"},{"name":"Shandong Provincial Clinical Research Center for Neurological Diseases  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Shandong Provincial Hospital, Shandong University  Jinan Shandong China"},{"name":"Department of Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"},{"name":"Shandong Provincial Clinical Research Center for Neurological Diseases  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology Shandong Provincial Hospital, Shandong University  Jinan Shandong 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