Résumé
We developed a highly sensitive and specific single-molecule array (Simoa) Homebrew assay for quantification of phosphorylated alpha-synuclein at serine 129 (pS129 alpha-syn) and evaluated its performance in human cerebrospinal fluid (CSF) and plasma. Using a cohort of patients with Parkinson's disease (PD), Alzheimer's disease (AD), and neurological controls with available CSF alpha-synuclein seed amplification assay (synSAA) outcome, we examined pS129 alpha-syn alongside N-terminal and C-terminal alpha-syn proteoforms. Our results showed that pS129 alpha-syn concentration was about 1% and 0.001% of the other alpha-syn species in CSF and plasma, respectively. We found no correlation between pS129 alpha-syn and synSAA outcome, indicating that soluble pS129 alpha-syn in CSF and plasma does not reflect presence of synucleinopathy. Interestingly, pS129 alpha-syn and other alpha-syn forms were significantly increased in AD compared to PD and controls, supporting the role of alpha-syn as biomarker of synaptic degeneration in AD.