Objective: To evaluate neurofilament light chain (NfL) as a longitudinal biomarker of disease burden and progression in Multiple System Atrophy and to explore its potential role in biomarker-driven disease staging.
Background: Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterised by autonomic failure, parkinsonism and/or cerebellar ataxia. Early diagnosis, prognostication and disease staging remain major unmet clinical needs. Neurofilament light chain has emerged as a promising marker of neuroaxonal injury, with prior studies demonstrating its association with disease severity, clinical progression and mortality in MSA.
Method: We are following a cohort of patients with MSA, performing serial measurements of NfL in both serum and cerebrospinal fluid. These biomarker measures are correlated with validated clinical outcomes including the Unified Multiple System Atrophy Rating Scale (UMSARS), patient-reported quality-of-life metrics and disease-duration survival to assess NfL as a dynamic marker of disease burden and progression.
Results: To date, longitudinal NfL measurements have been obtained in 71 patients. Clinical phenotypes include undefined MSA (n=43), MSA with predominant cerebellar features (MSA-C, n=20) and MSA with predominant parkinsonism (MSA-P, n=30). In parallel, we are integrating high-sensitivity proteomic profiling using NULISAseq with alpha-synuclein seed amplification assays in a subset of patients (68 clinically probable MSA, including 8 pathology-confirmed cases). These multimodal biomarker datasets will be used to model disease trajectories and evaluate the ability of fluid biomarkers to predict clinical outcomes and improve diagnostic accuracy.
Conclusion: By combining longitudinal clinical data with fluid biomarker profiling, this work aims to develop a biologically informed staging framework for MSA capable of identifying early disease, tracking progression and supporting patient stratification for future clinical trials.
To cite this abstract in AMA style:
L. Lei, R. Lee, P. Korlipara, V. Chelban, H. Houlden. Towards Biomarker-Driven Staging of Multiple System Atrophy Using Longitudinal Neurofilament Light Profiling [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/towards-biomarker-driven-staging-of-multiple-system-atrophy-using-longitudinal-neurofilament-light-profiling/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/towards-biomarker-driven-staging-of-multiple-system-atrophy-using-longitudinal-neurofilament-light-profiling/