CSF α-synuclein inversely correlates with non-motor symptoms in a cohort of PD patients

Introduction: Although non-motor symptoms are early and disabling features of PD, reliable predictors and effective therapies are not yet available. Measurement of CSF proteins mirroring brain pathology is currently utilized for diagnostic and prognostic clustering of patients with neurodegenerative diseases but the association with non-motor symptoms in PD has not been evaluated. Here we performed a cross-sectional correlation study, aimed at identifying potential fluid biomarkers for non-motor symptoms in PD.Methods: CSF levels of 42-amyloid-beta, total and phosphorylated tau, alpha-synuclein and reciprocal ratios were measured in a group of 46 PD patients compared to 37 gender/age-matched controls and correlated with standard clinical scores for motor and non-motor features.Results: We observed that alpha-synuclein levels were reduced in PD (p < 0.05, AUC = 0.8; p < 0.05) and inversely correlated with non-motor symptoms scale total score and items 3 and 9, even independently from age, disease duration, motor impairment severity and dopaminergic treatment (T = -2,9, p < 0.014; T = -3.6, p < 0.05; item 9: T = -2.1, p < 0.05, respectively).Conclusions: Our findings suggest that the reduction of CSF alpha-synuclein may parallel degeneration of non-dopaminergic systems. Although confirmatory studies are necessary, CSF alpha-synuclein reduction might represent a potential biomarker to monitor non-motor symptoms burden.