Increased activity of Piezo1 channel in red blood cells is associated with Alzheimer's disease-related dementia

Abstract

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.

Keywords: Alzheimer's disease; Ca‐imaging; Piezo1; RBC.