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Related Experiment Video

Updated: May 9, 2025

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Neuronal α-Synuclein Disease Stage Progression over 5 Years.

Tanya Simuni1, Caroline Gochanour2, Anuprita R Nair2

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Movement Disorders : Official Journal of the Movement Disorder Society
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Summary
This summary is machine-generated.

The Neuronal α-synuclein disease integrated staging system (NSD-ISS) effectively tracks disease progression over five years in early stages. This staging system shows promise as a research tool for developing new treatments for neurodegenerative diseases.

Keywords:
Parkinson's diseasebiological definitiondementia with Lewy bodiesneuronal α‐synuclein disease

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Area of Science:

  • Neurology
  • Biomarker research
  • Neurodegenerative disease research

Background:

  • Neuronal α-synuclein disease (NSD) is characterized by in vivo biomarkers of neuronal alpha-synuclein (n-asyn) pathology.
  • The Neuronal α-synuclein disease integrated staging system (NSD-ISS) categorizes disease progression from stages 0 to 6.

Purpose of the Study:

  • To evaluate the 5-year longitudinal changes in the NSD-ISS within early-stage disease.
  • To assess the utility of NSD-ISS in tracking disease progression in Parkinson's disease (PD) patients, prodromal PD patients, and healthy controls (HC).

Main Methods:

  • Analysis of a subset of participants from the Parkinson's Progression Markers Initiative (PPMI) meeting NSD criteria.
  • Annual staging over 5 years based on n-asyn biomarkers, dopaminergic dysfunction, clinical features, and functional impairment.
  • Inclusion of PD patients, prodromal PD patients, and HCs enrolled before 2020.

Main Results:

  • At baseline, most participants were in stages 2B (24%), 3 (56%), or 4 (13%).
  • After 5 years, stage distribution shifted, with increased percentages in stages 3 (50%) and 4 (34%), indicating progression.
  • Progression drivers included motor and non-motor functional impairments, with dopaminergic medication initiation causing stage regression in some participants.

Conclusions:

  • The NSD-ISS is valuable for defining early-stage disease progression (stages 2B, 3, 4) and serves as a potential research tool for drug development.
  • Further investigation with preclinical cohorts is recommended to fully establish the NSD-ISS.
  • The study supports the utility of NSD-ISS in research for neurodegenerative diseases like Parkinson's.