Association of αS-SAA kinetics with clinical scores in the clinical spectrum of Parkinson's disease

Background: Cerebrospinal fluid (CSF) α-synuclein seed amplification assay (αS-SAA) is a recognized biomarker of synucleinopathy. In Parkinson's disease (PD), its potential for predicting clinical outcome needs to be further assessed. Objective: To evaluate the associations between clinical outcome and αS-SAA kinetic parameters in a retrospective cohort of PD patients, also investigating whether CSF total protein content influences such associations. Methods: Study cohort included cognitively unimpaired PD (PD-CN, n = 40), PD with mild cognitive impairment (PD-MCI, n = 44), and PD with dementia (PDD, n = 10) with available clinical assessment at baseline. Among them, n = 28 PD-CN and n = 31 PD-MCI patients had 2-year follow-up, and CSF biomarkers reflecting pathophysiological pathways other than synucleinopathy. Results: In PD-MCI, αS-SAA time-to-threshold (TTT) is associated with longitudinal changes in Mini-Mental State Examination. The association is stronger when accounting for CSF total protein concentration. Conclusions: αS-SAA TTT may represent a prognostic factor for cognitive decline in PD-MCI.