Cerebrospinal α-Synuclein Oligomers Reflect Disease Motor Severity in DeNoPa Longitudinal Cohort

Background Tangible efforts have been made to identify biomarkers for Parkinson's disease (PD) diagnosis and progression, with alpha-synuclein (alpha-syn) related biomarkers being at the forefront. Objectives The objectives of this study were to explore whether cerebrospinal fluid (CSF) levels of total, oligomeric, phosphorylated Ser 129 alpha-synuclein, along with total tau, phosphorylated tau 181, and beta-amyloid 1-42 are (1) informative as diagnostic markers for PD, (2) changed over disease progression, and/or (3) correlated with motor and cognitive indices of disease progression in the longitudinal De Novo Parkinson cohort. Methods A total of 94 de novo PD patients and 52 controls at baseline and 24- and 48-month follow-up were included, all of whom had longitudinal lumbar punctures and clinical assessments for both cognitive and motor functions. Using our in-house enzymelinked immunosorbent assays and commercially available assays, different forms of alpha-synuclein, tau, and beta-amyloid 1-42 were quantified in CSF samples from the De Novo Parkinson cohort. Results Baseline CSF total alpha-synuclein was significantly lower in early de novo PD compared with healthy controls, whereas the ratio of oligomeric/total and phosphorylated/total were significantly higher in the PD group. CSF oligomeric-alpha-synuclein longitudinally increased over the 4-year follow-up in the PD group and correlated with PD motor progression. Patients at advanced stages of PD presented with elevated CSF oligomeric-alpha-synuclein levels compared with healthy controls. Conclusions Longitudinal transitions of CSF biomarkers over disease progression might not occur linearly and are susceptible to disease state. CSF oligomeric-alpha-synuclein levels appear to increase with diseases severity and reflect PD motor rather than cognitive trajectories. (c) 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Automated summary

This study investigated CSF biomarkers levels in newly diagnosed Parkinson's disease patients, finding that CSF oligomeric alpha-synuclein increased with disease severity and reflected PD motor trajectories.