Evaluating the Role of α-Synuclein Seed Amplification as a Disease Progression Marker: Evidence and Uncertainties.
Evaluating the Role of α-Synuclein Seed Amplification as a Disease Progression Marker: Evidence and Uncertainties.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
London, GB · Author affiliation
Centre for Preventive Neurology, Wolfson Institute of Population Health, Faculty of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.Location evidence
Rio Grande, BR · Author affiliation
Machine Learning Theory and Application Research Laboratory, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.Location evidence
Porto Alegre, BR · Author affiliation
Machine Learning Theory and Application Research Laboratory, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.Location evidence
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Original abstract
BACKGROUND: α-synuclein seeding amplification assay (α-synuclein SAA) development as a diagnostic biomarker for Parkinson's disease (PD) has shown promising results over the past decade. However, the utility of these assays in the prediction of disease progression is unclear. OBJECTIVES: To assess the relationship between α-synuclein SAA and PD-specific clinical outcome measures. METHODS: We extracted longitudinal data on individuals with sporadic PD from the Parkinson's Progression Markers Initiative at baseline and 5 years follow-up. Primary outcome measures included MDS-UPDRS Part III, Montreal Cognitive Assessment (MoCA) and L-dopa equivalent daily dose (LEDD). Secondary outcome measures included REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) question-6 and other non-motor assessments. α-synuclein SAA kinetic parameters were added to linear regression models to assess their impact on model fit. RESULTS: We included 279 participants in the final analysis. There was no consistent evidence that α-synuclein SAA parameters at baseline improved our prediction models for MDS-UPDRS Part III, MoCA or LEDD at 5 years. α-synuclein SAA kinetic parameters improved model fit for RBDSQ question-6 and indicated that fast seeding profiles were associated with higher scores. CONCLUSIONS: We did not find evidence of a relationship between α-synuclein SAA and disease progression however α-synuclein SAA was associated with RBDSQ. Further work is needed to understand the factors influencing α-synuclein aggregation kinetics and the role of α-synuclein SAA in disease prognosis.