Sitnikova Valeriia, Nurkhametova Dilyara, Braidotti Nicoletta, Ciubotaru Catalin D, Giudice Luca, Impola Ulla, Kärkkäinen Sari, Kalapudas Juho, Penttilä Elina, Löppönen Heikki, Fagerlund Ilkka, Kanninen Katja M, Zetterberg Henrik, Kokkola Tarja, Laitinen Saara, Koivisto Anne, Cojoc Dan, Giniatullin Rashid, Malm Tarja M
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Materials Foundry, National Research Council of Italy (CNR-IOM), Area Science Park Basovizza, Trieste, Italy.
Alzheimers Dement. 2025 Jun;21(6):e70368. doi: 10.1002/alz.70368.
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.
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.
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.
Our data suggest that Yoda1-induced Ca flux through Piezo1 channel emerges as a measurable indicator associated with and improves the detection of AD-related dementia.
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.
红细胞（RBCs）对于向活跃组织输送氧气至关重要，并在微循环床中承受巨大的机械力。与细胞骨架相连的机械敏感Piezo1通道的富集有助于红细胞在狭窄的毛细血管中穿行。在阿尔茨海默病（AD）中，脑微循环受损可能需要增强红细胞中Piezo1的功能。
我们使用微量移液器抽吸和流式细胞术技术，通过特异性Piezo1激动剂Yoda1，评估了认知健康患者（HC）、轻度认知障碍（MCI）患者和AD患者红细胞生物力学特性的AD相关改变。
我们发现β-淀粉样蛋白（Aβ）肽会改变红细胞的生物力学特性。我们观察到，与年龄匹配的HC患者的红细胞相比，MCI患者和AD患者的红细胞对Yoda1诱导的钙反应明显更高。
我们的数据表明，Yoda1诱导的通过Piezo1通道的钙通量是一种与AD相关痴呆相关的可测量指标，并改善了对其的检测。
Piezo1通道有助于红细胞在狭窄的毛细血管中穿行。阿尔茨海默病（AD）患者红细胞中Yoda1诱导的Piezo1激活增加。纳入Yoda1诱导的Piezo1读数改善了对AD相关痴呆的检测。研究与早期AD相关的Yoda1诱导的Piezo1活性。
