Elevated α‐Synuclein Aggregate Levels in the Urine of Patients with Isolated REM Sleep Behavior Disorder and Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative disorder characterized by α‐synuclein aggregation in neurons. Recent advances suggest α‐synuclein aggregates could serve as a biomarker for PD and related synucleinopathies. This study used surface‐based fluorescence intensity distribution analysis (sFIDA) to measure α‐synuclein aggregates in urine. Patients with PD and isolated rapid eye movement sleep behavior disorder, a precursor to PD, had elevated concentrations compared with healthy controls. Sensitivity and specificity were 83% and 65% for PD versus controls and 89% and 62% for isolated rapid eye movement sleep behavior disorder versus controls. The findings highlight sFIDA's potential for diagnosing synucleinopathies. ANN NEUROL 2025;98:147–151