Objective: To evaluate the association between PD non-motor symptoms (NMS) and CSF levels of neurodegeneration-related proteins in a population of PD patients, aimed at identifying reliable biomarkers for NMS.

Background: NMS often precede motor signs (MS) and progress along the course of PD, leading to severe disability and poor quality of life in patients. Despite such clinical relevance, NMS still lack of effective therapies and reliable predictors. CSF proteins mirror brain pathological changes, thus representing useful biomarkers for diagnosis and prognostic clustering of patients with neurodegenerative diseases.

Methods: Demographic, biochemical and clinical data were prospectively collected from 46 PD patients and compared to 37 age/sex matched healthy controls (CTL). CSF quantitative analysis included total alpha-synuclein (a-syn), amyloid-beta-42 (Ab42), total and phosphorylated tau (t-tau, p-tau), Ab42/p-tau, p-tau/t-tau, t-tau/a-syn+Ab42, p-tau/a-syn+Ab42 ratios. In PD group, clinical assessment consisted of MMSE, UPDRS pars 2-3, NMS scale (NMSS, total and subitems scores), levodopa equivalent dose (LED) calculation. Parametric and non-parametric tests were conducted to evaluate differences between the groups. The ROC curve analysis with cut-off point calculation was further run. Spearman’ test and subsequent linear regression analysis (using age, disease duration and LED as covariates) were applied to test the association between biomarkers and clinical scores.

Results: a-syn, t-tau and p-tau/t-tau ratio levels were lower in PD than CTL, independently from age and gender. a-syn was inversely related to NMSS, either total or items 3-9 scores, independently from age, disease duration and LED.

Conclusions: In this cohort of PD patients, total a-syn CSF levels were inversely and independently related to NMS, in the absence of significant correlations with MS. We thus preliminarily suggest that CSF a-syn may reflect synuclein-related degeneration of non-dopaminergic neuronal networks, supporting the use as a biomarker to predict and/or monitor NMS burden.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/total-csf-alpha-synuclein-is-inversely-associated-with-non-motor-symptoms-in-a-population-of-patients-with-parkinsons-disease/