Correlated levels of cerebrospinal fluid pathogenic proteins in drug-naive Parkinson's disease

Background and aimToxic oligomeric -synuclein (S; O-S) has been suggested to play a central role in the pathogenesis of Lewy body diseases such as Parkinson's disease (PD). Cerebrospinal fluid (CSF) levels of S, O-S, total and phosphorylated tau, and amyloid 1-42 (A1-42) are thought to reflect the pathophysiology or clinical symptoms in PD. In this study, we examined correlations of the CSF levels of these proteins with the clinical symptoms, and with each other in drug-naive patients with PD.MethodsTwenty-seven drug-naive patients with PD were included. Motor and cognitive functions were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), and Neurobehavioral Cognitive Status Examination (COGNISTAT). CSF levels of total S, O-S, A1-42, total tau and tau phosphorylated at threonine 181 (P-tau181p) were measured. CSF levels of these proteins were compared with clinical assessments from the UPDRS, MoCA and COGNISTAT using Spearman correlation analysis. Spearman correlation coefficients among CSF protein levels were also evaluated.ResultsCSF levels of S were negatively correlated with UPDRS part III (motor score) (p<0.05) and bradykinesia (p<0.01), and positively correlated with COGNISTAT subtest of judgement (p<0.01) and CSF levels of A1-42 (p<0.001), total tau (p<0.001) and P-tau181p (p<0.01). Lower CSF levels of A1-42, total tau and P-tau181p were significantly related to worsening of some motor and/or cognitive functions. The CSF level of O-S showed no correlation with any motor and cognitive assessments or with CSF levels of the other proteins.ConclusionCSF levels of S are correlated with some clinical symptoms and CSF levels of other pathogenic proteins in drug-naive PD patients. These correlations suggest a central role for interaction and aggregation of S with A1-42, tau, and phosphorylated tau in the pathogenesis of PD. Although O-S has been shown to have neurotoxic effects, CSF levels do not reflect clinical symptoms or levels of other proteins in cross-sectional assessment.