Neuronal α-Synuclein Disease Stage Progression over 5 Years

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.