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The enrichment of mechanosensitive Piezo1 channels, linked to the cytoskeleton, aids RBCs in navigating the narrow capillaries. In Alzheimer's disease (AD), impaired brain microcirculation may necessitate enhanced Piezo1 function in RBCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>With micropipette aspiration and flow cytometry technics, we evaluated, using the specific Piezo1 agonist Yoda1, AD\u2010related alterations in the biomechanical properties of RBCs from cognitively healthy patients (HC) and individuals with mild cognitive impairment (MCI) and AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>We show that beta\u2010amyloid (A\u03b2) peptides alter the biomechanical properties of RBCs. We observed significantly higher Yoda1\u2010induced calcium responses in RBCs in individuals with MCI and AD compared to RBCs from age\u2010matched HC.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Our data suggest that Yoda1\u2010induced Ca<jats:sup>2+<\/jats:sup> flux through Piezo1 channel emerges as a measurable indicator associated with and improves the detection of AD\u2010related dementia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Piezo1 channels aid the navigation of red blood cells (RBCs) through narrow capillaries.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Alzheimer's disease (AD) patients show increased Yoda1\u2010induced activation of Piezo1 in RBCs.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Incorporation of Yoda1\u2010induced Piezo1 readouts improved the detection of AD\u2010related dementia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Investigating Yoda1\u2010induced Piezo1 activity associated with early AD.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70368","type":"journal-article","created":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T10:39:28Z","timestamp":1751193568000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Increased activity of Piezo1 channel in red blood cells is associated with Alzheimer's disease\u2010related dementia"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8192-1236","authenticated-orcid":false,"given":"Valeriia","family":"Sitnikova","sequence":"first","affiliation":[{"name":"A.I.\u00a0 Virtanen Institute for Molecular Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilyara","family":"Nurkhametova","sequence":"additional","affiliation":[{"name":"A.I.\u00a0 Virtanen Institute for Molecular Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Braidotti","sequence":"additional","affiliation":[{"name":"Materials Foundry National Research Council of Italy (CNR\u2010IOM) Area Science Park Basovizza  Trieste Italy"},{"name":"Department of Physics University of Trieste  Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalin D.","family":"Ciubotaru","sequence":"additional","affiliation":[{"name":"Materials Foundry National Research Council of Italy (CNR\u2010IOM) Area Science Park Basovizza  Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Giudice","sequence":"additional","affiliation":[{"name":"A.I.\u00a0 Virtanen Institute for Molecular Sciences University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulla","family":"Impola","sequence":"additional","affiliation":[{"name":"Research and Development Finnish Red Cross Blood Service  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sari","family":"K\u00e4rkk\u00e4inen","sequence":"additional","affiliation":[{"name":"Biomarker Laboratory Institute of Clinical Medicine\/Neurology University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juho","family":"Kalapudas","sequence":"additional","affiliation":[{"name":"Neuro Centre Kuopio University Hospital  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Penttil\u00e4","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology School of Medicine University of Eastern Finland and Kuopio University 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