Plasma Neurofilament Light Chain and TNF-alpha Correlate with Motor Features in Isolated REM Sleep Behavior Disorder

Abstract

Background: Isolated RBD (iRBD) is a prominent early marker of Parkinson's disease and related disorders. Objective(s): Evaluate biomarkers of inflammation and axonal damage people with iRBD for disease progression. Method(s): Plasma samples from 27 video-polysomnography confirmed iRBD patients and 25 controls were analyzed for inflammatory biomarkers (CRP, IL-6, TNF-alpha, IFN-gamma, IL-1beta) and NfL using the Meso Scale Discovery platform. Result(s): People with iRBD had elevated plasma TNF-alpha and IL-6 (p = 0.013 and p = 0.051). In the iRBD group, plasma NfL was associated with objective motor tests: Timed Up and Go (R2 = 0.292, p = 0.027) and 10-m walk (R2 = 0.355, p = 0.034) and plasma TNF-alpha was associated with the Timed Up and Go test (R2 = 0.277, p = 0.025). Conclusion(s): We report evidence of peripheral inflammation in early synuclein-related disease processes, and association of plasma NfL and TNF-alpha with motor dysfunction in iRBD patients, suggesting possible association with increased risk of phenoconversion. Copyright © 2025 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.