Quantification of cerebrospinal fluid α-synuclein seeds by endpoint dilution seed amplification assay in Parkinson’s disease

Quantitative pathology-specific biomarkers are needed for patients with Parkinson's disease (PD). We estimated the α-syn seeding dose giving 50% of positive seed amplification assay (SAA) reactions (SD50) in serially diluted samples from 260 PD participants, of whom 54 had longitudinal samples. We then evaluated the associations between SD50 values and demographic and clinical parameters, including motor and cognitive scales, REM sleep behaviour disorder (RBD), and hyposmia. Higher SD50 values were significantly associated with older age, longer disease duration, worse motor and cognitive scores, and presence of RBD and visual hallucinations. Baseline SD50 values predicted the development of motor wearing-off and severe cognitive impairment. In participants with longitudinal samples, SD50 values remained substantially stable over time. Quantification of α-syn through endpoint dilution SAA may serve as a potential surrogate marker of LB pathological burden, which may support prognostication and patient stratification.