Assessment of Piezo1 Expression in Urinary Exfoliated Cells as a Diagnostic Indicator for Multiple System Atrophy

Abstract Background Multiple system atrophy (MSA) shares clinical features with idiopathic Parkinson’ s disease (iPD) and progressive supranuclear palsy (PSP), yet reliable biomarkers for differential diagnosis remain elusive. Objectives This study aimed to evaluate Piezo1/2 expression in urinary exfoliated cells as a potential biomarker for MSA differentiation. Methods Piezo1/2 expression levels were quantified in urinary exfoliated cells from 76 MSA patients, 103 iPD patients, 59 PSP patients, and 126 healthy controls (HCs) across three independent cohorts using multiple analytical techniques. Results In the discovery cohort, Piezo1 expression was significantly reduced in MSA patients compared with HCs, iPD, and PSP (area under the curve: 0.9421, 0.8218, and 0.8036, respectively). These findings were validated in two independent cohorts, confirming consistently lower Piezo1 levels in MSA patients and their utility in distinguishing MSA from other groups. Conclusion Reduced Piezo1 levels in urinary exfoliated cells show strong potential as a non‐invasive biomarker for diagnosing MSA. © 2025 International Parkinson and Movement Disorder Society.