ArticleMovement disorders : official journal of the Movement Disorder Society2025
Neuronal α-Synuclein Disease Stage Progression over 5 Years.
Article in Movement disorders : official journal of the Movement Disorder Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Machine Learning Prediction of Hoehn and Yahr Scores at 5-Years Post-Movement disorders clinical practice · 2026Article
- Disease modification in advanced Parkinson's disease: a review and roadmap for paving the way for next-generation interventions.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- A Biological Framework for Parkinson's Disease: Advances in α-Synuclein-Centered Biomarkers and Staging.Journal of neurochemistry · 2026Review
- Reply to: "Refutation of the αSyn-SAA-Based Staging for Parkinson's Progression (Neuronal α-Synuclein Disease-Integrated Staging System [NSD-ISS])".Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Refutation of the αSyn-SAA-Based Staging for Parkinson's Progression (Neuronal α-Synuclein Disease-Integrated Staging System [NSD-ISS]).Movement disorders : official journal of the Movement Disorder Society · 2025Article
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20 authors.
Funding
Abstract
backgroundNeuronal α-synuclein disease (NSD) is defined by the presence of an in vivo biomarker of neuronal alpha-synuclein (n-asyn) pathology. The NSD integrated staging system (NSD-ISS) for research describes progression across the disease continuum as stages 0 to 6.
objectiveThe aim was to assess 5-year longitudinal change in NSD-ISS in early disease.
methodsAnalysis included a subset of participants from the Parkinson's Progression Markers Initiative (PPMI) enrolled before 2020 as Parkinson's disease (PD) patients, prodromal PD patients, or healthy controls (HC) who met NSD criteria. Staging was defined based on biomarkers of n-asyn and dopaminergic dysfunction in early stages, clinical features, and severity of functional impairment in stages 3 to 6. Stages were determined annually for 5 years.
resultsOf 576 NSD participants, 494 were enrolled as PD patients, 74 prodromal PD patients, and 8 HCs. At baseline, 24% of participants were stage 2B, 56% Stage 3, 13% stage 4, and less than 5% in other stages. At year 5, the respective percentages for stages 2B to 4 were 11%, 50%, and 34%, indicating progression through NSD stages. Progression was driven by functional impairment in the predominantly motor domain (95%) for stage 2B to 3, increasing degree of nonmotor dysfunction for stages 3 to 4 (46%), and a combination of domains for stages 4 to 5. Initiation of dopaminergic medications led to stage regression in 8% of participants in Stage 3 but 41% in stage 4.
conclusionsOur analysis supports the utility of NSD-ISS in defining the stages of disease progression, at least in the early clinical and prodromal stages (2B, 3, or 4), suggesting the value of NSD-ISS as a potential research tool for drug development. Further research involving preclinical cohorts is a crucial next step. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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