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Here, we investigated whether systemic activation of the mechanosensitive ion channel Piezo1 affects cerebrovascular deficits in an AD mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Using two\u2010photon in vivo imaging and laser\u2010speckle imaging, we determined CBF, capillary stalling, and FH in the 5xFAD model of AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We observed increased capillary stalling and reduced CBF and FH to whisker stimulation in 5xFAD mice compared to wild\u2010type controls. The systemic administration of the Piezo1 agonist Yoda1 led to a \u2248 65% reduction in capillary stalls, increased CBF, and significantly improved FH in response to whisker stimulation, restoring CBF responses in 5xFAD mice to levels comparable to controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These results suggest that Piezo1 activation improves microvascular flow and neurovascular coupling in AD, highlighting Piezo1 as a promising therapeutic target for early cerebrovascular dysfunction during AD.<\/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>An Alzheimer's disease (AD) animal model demonstrates reduced brain capillary blood flow and impaired neurovascular coupling.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Pharmacological activation of Piezo1 at the systemic level improves blood flow and functional hyperemia during AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Piezo1 is involved in cerebrovascular dysfunction associated with AD<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71016","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T06:45:45Z","timestamp":1765867545000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Systemic Piezo1 activation improves cerebrovascular function in Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Zeynab","family":"Tabrizi","sequence":"first","affiliation":[{"name":"Department of Biology University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin Rui","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Larner College of Medicine Vermont Center for Cardiovascular and Brain Health University of Vermont  Burlington Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supriya","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Biology University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2061-1100","authenticated-orcid":false,"given":"Osama F.","family":"Harraz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Larner College of Medicine Vermont Center for Cardiovascular and Brain Health University of Vermont  Burlington Vermont USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9414-6590","authenticated-orcid":false,"given":"Oliver","family":"Bracko","sequence":"additional","affiliation":[{"name":"Department of Biology University of Miami  Miami Florida USA"},{"name":"Department of Neurology University of Miami Miller School of Medicine  Miami Florida 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