Valeriia Sitnikova, Dilyara Nurkhametova, Nicoletta Braidotti, Catalin D. Ciubotaru, Luca Giudice, Ulla Impola, Sari Kärkkäinen, Juho Kalapudas, Elina Penttilä, Heikki Löppönen, Ilkka Fagerlund, Katja M. Kanninen, Henrik Zetterberg, Tarja Kokkola, Saara Laitinen, Anne Koivisto, Dan Cojoc, Rashid Giniatullin, Tarja M. Malm
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In Alzheimer's disease (AD), impaired brain microcirculation may necessitate enhanced Piezo1 function in RBCs.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>With micropipette aspiration and flow cytometry technics, we evaluated, using the specific Piezo1 agonist Yoda1, AD-related alterations in the biomechanical properties of RBCs from cognitively healthy patients (HC) and individuals with mild cognitive impairment (MCI) and AD.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>We show that beta-amyloid (Aβ) peptides alter the biomechanical properties of RBCs. We observed significantly higher Yoda1-induced calcium responses in RBCs in individuals with MCI and AD compared to RBCs from age-matched HC.</p>\n </section>\n \n <section>\n \n <h3> CONCLUSION</h3>\n \n <p>Our data suggest that Yoda1-induced Ca<sup>2+</sup> flux through Piezo1 channel emerges as a measurable indicator associated with and improves the detection of AD-related dementia.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Piezo1 channels aid the navigation of red blood cells (RBCs) through narrow capillaries.</li>\n \n <li>Alzheimer's disease (AD) patients show increased Yoda1-induced activation of Piezo1 in RBCs.</li>\n \n <li>Incorporation of Yoda1-induced Piezo1 readouts improved the detection of AD-related dementia.</li>\n \n <li>Investigating Yoda1-induced Piezo1 activity associated with early AD.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 6","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70368","citationCount":"0","resultStr":"{\"title\":\"Increased activity of Piezo1 channel in red blood cells is associated with Alzheimer's disease-related dementia\",\"authors\":\"Valeriia Sitnikova, Dilyara Nurkhametova, Nicoletta Braidotti, Catalin D. 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Increased activity of Piezo1 channel in red blood cells is associated with Alzheimer's disease-related dementia
INTRODUCTION
Red blood cells (RBCs) are crucial for oxygen delivery to active tissues and endure significant mechanical forces in the microcirculatory bed. 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.
METHODS
With micropipette aspiration and flow cytometry technics, we evaluated, using the specific Piezo1 agonist Yoda1, AD-related alterations in the biomechanical properties of RBCs from cognitively healthy patients (HC) and individuals with mild cognitive impairment (MCI) and AD.
RESULTS
We show that beta-amyloid (Aβ) peptides alter the biomechanical properties of RBCs. We observed significantly higher Yoda1-induced calcium responses in RBCs in individuals with MCI and AD compared to RBCs from age-matched HC.
CONCLUSION
Our data suggest that Yoda1-induced Ca2+ flux through Piezo1 channel emerges as a measurable indicator associated with and improves the detection of AD-related dementia.
Highlights
Piezo1 channels aid the navigation of red blood cells (RBCs) through narrow capillaries.
Alzheimer's disease (AD) patients show increased Yoda1-induced activation of Piezo1 in RBCs.
Incorporation of Yoda1-induced Piezo1 readouts improved the detection of AD-related dementia.
Investigating Yoda1-induced Piezo1 activity associated with early AD.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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