Diagnostic and prognostic value of α-synuclein seed amplification assay kinetic measures in Parkinson's disease: a longitudinal cohort study
Abstract
BACKGROUND
α-synuclein seed amplification assay (SAA) positivity has been proposed as a diagnostic biomarker for Parkinson's disease. However, studies of the prognostic value of this biomarker have been limited to small, single-centre studies over short follow-up periods. We aimed to assess the diagnostic and prognostic value of quantitative CSF α-synuclein SAA kinetic measures in Parkinson's disease.
METHODS
In this longitudinal cohort study, we collected and analysed data from participants with Parkinson's disease, progressive supranuclear palsy, and healthy controls enrolled in three cohorts: the UK parkinsonism cohort, the Parkinson's Progression Markers Initiative (PPMI) international observational study, and the Tübingen Parkinson's disease cohort. Baseline CSF α-synuclein SAA data and longitudinal clinical data were collected between Jan 1, 2005, and Nov 1, 2023. The following seeding kinetic measures were calculated from the α-synuclein SAA curve for each SAA-positive sample: time to threshold (TTT) for a positive SAA result; maximum Thioflavin T fluorescence during the reaction time (MaxThT); and area under the fluorescence curve during the reaction time (AUC). We compared seeding kinetic measures between sporadic Parkinson's disease and progressive supranuclear palsy, and between sporadic Parkinson's disease and monogenic Parkinson's disease. We used time-to-event analyses to assess the ability of α-synuclein SAA kinetic measures to predict an unfavourable outcome…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 1,631 participants or records.
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