Predicting CSF α-Synuclein Seed Amplification Assay Status From Demographics and Clinical Data.

Background and Objective: The alpha-synuclein (α-syn) cerebrospinal fluid seed amplification assay (CSF SAA) presents a promising diagnostic for Parkinson's disease (PD) and other synucleinopathies. The objective of this study was to develop and externally validate models to predict probabilities of α-syn positive or negative status in vivo in a mixture of people with and without PD using easily accessible clinical predictors. Methods: Uni- and multi-variable logistic regression models were developed in a cohort of participants from the Parkinson Progression Marker Initiative (PPMI) study to predict CSF α-syn status as measured by SAA. Models were externally validated in a cohort of participants from the Systemic Synuclein Sampling Study (S4) that had also measured CSF α-syn status using SAA. Results: The PPMI model training/testing cohort included 1260 participants, 37% of whom were female, and a mean (± standard deviation) age of 62.4 (±10.0) years. Among them, 76% had manifest PD with a mean disease duration of 1.2 (±1.6) years. Overall, 68.7% of the overall PPMI cohort (and 88.0% with PD of those with manifest PD) had positive CSF α-syn SAA status results. Variables from the full multivariable model to predict CSF α-syn SAA status included age- and sex-specific University of Pennsylvania Smell Identification Test (UPSIT) percentile values, sex, self-reported frequency of constipation problems, leucine-rich repeat kinase 2 ( Conclusion: Data-driven models using non-invasive clinical features can accurately predict CSF α-syn SAA positive and negative status in cohorts enriched for people living with PD. Scores from the UPSIT were highly significant in predicting α-syn SAA status.