Objective: This study aims to assess plasma NfL levels in iRBD and their utility in detecting early neurodegenerative changes.
Background: Rapid-Eye-Movement (REM) sleep behavior disorder (RBD) is a recognized prodromal marker of α-synucleinopathies, including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Isolated RBD (iRBD) provides a unique population for studying early biomarkers of neurodegeneration. Among these, neurofilament light chain protein (NfL), a neuron-specific axonal marker, shows promise for tracking disease progression.
Method: A total of 178 participants aged-matched [PD: 54 (M:39, F:15); iRBD: 54 (M:47, F:7); MSA: 16 (M:9, F:7); HC: 54 (M:34, F:20)]were enrolled and underwent comprehensive clinical evaluations at the Mondino Foundation and Univeristy Hospital of Pisa. Plasma NfL levels were measured at the Mondino Foundation using the Ella platform.
Results: Plasma NfL levels were significantly elevated in PD and MSA compared to HC (PD vs. HC p=0.0001; MSA vs. HC p<0.0001). iRBD patients also exhibited significantly higher NfL levels than HC (p=0.0020) and lower levels than MSA (p=0.0002). No significant difference was observed between PD and iRBD (p=0.5848). Within the iRBD group, those with orthostatic hypotension (OH) showed significantly higher NfL levels (p=0.0114), while no differences were observed based on hyposmia, constipation, or cognitive impairment. Plasma NfL levels did not correlate with MDS-UPDRS-III scores in iRBD patients.
Conclusion: Elevated plasma-NfL levels in iRBD reflect early axonal damage, aligning with the presence of ongoing neurodegeneration. The association between OH and higher NfL levels suggests a potential association with MSA, where autonomic dysfunction is a defining feature. This observation warrants further longitudinal studies to validate our hypothesis. Plasma NfL holds promise as a biomarker for CNS damage, offering valuable insights into the progression and differentiation of α-synucleinopathies when integrated with clinical data.
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To cite this abstract in AMA style:
A. Calculli, D. Di Martino, P. Grillo, G. Bellini, C. Fazio, D. Comolli, D. Hoxhaj, S. Cerri, M. Terzaghi, A. Pisani. Plasma Neurofilament Light Chain and Orthostatic Hypotension in Isolated REM Sleep Behavior Disorder: A Biomarker for α-Synucleinopathy Progression [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/plasma-neurofilament-light-chain-and-orthostatic-hypotension-in-isolated-rem-sleep-behavior-disorder-a-biomarker-for-%ce%b1-synucleinopathy-progression/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/plasma-neurofilament-light-chain-and-orthostatic-hypotension-in-isolated-rem-sleep-behavior-disorder-a-biomarker-for-%ce%b1-synucleinopathy-progression/