Synaptic proteins in CSF relate to Parkinson's disease stage markers

Abstract

Recent findings of morphological and functional changes in Parkinson's disease brains have shown altered synapse formation, but their role in cognitive decline is still an area under exploration. Here we measured the concentration of three key synaptic proteins, Rab3A, SNAP25 and neurogranin by enzyme-linked immunosorbent assay, in cerebrospinal fluid from a total of 139 participants (87 controls and 52 Parkinson's disease patients out of which 30 were drug-naïve) and explored their associations with motor and cognitive symptoms. Associations with motor disease stage (assessed by Hoehn and Yahr scale) and cognitive performance (assessed by the Montreal Cognitive Assessment scores) were explored. An overall increase in the concentration of SNAP25 was found in Parkinson's disease patients (p = 0.032). Increased neurogranin levels were found in the drug naïve patients subgroup (p = 0.023). Significant associations were observed between increased concentration of neurogranin and cognitive impairment in total Parkinson's disease group (p = 0.017), as well as in the drug naïve (p = 0.021) and with motor disease stage (p = 0.041). There were no significant disease-driven changes observed in the concentration of Rab3a. Concentrations SNAP25 and neurogranin were increased in cerebrospinal fluid of Parkinson's disease patients in a disease specific manner and related to cognitive and motor symptom severity. Future longitudinal studies should explore whether cerebrospinal fluid synaptic proteins can predict cognitive decline in Parkinson's disease.

Fig. 1

Changes in the CSF concentration of synaptic proteins neurogranin, Rab3A and SNAP25 and their clinical correlates. Concentration of synaptosome associated protein SNAP25 (b) measured by ELISA present overall increase in the PD patient group while presynaptic vesicle protein Rab3A (a) and postsynaptic protein neurogranin (c) concentrations remained unchanged in CSF of patients diagnosed with Parkinson disease compared to control participants. In the subgroup of drug naïve patients concentrations of neurogranin were elevated compared to control patients. Statistical analyses were performed using Mann-Whitney U test. p-value < 0.05 was considered significant. Neurogranin protein concentration presents significant negative correlation with cognitive impairment of PD patients assessed by MoCA scores. There were no significant correlations observed between Rab3A or SNAP25 and cognitive assessment. Neurogranin presented significant correlation with disease stage. There were no significant associations between disease stage and presynaptic proteins. The bars represent the mean values with inter-quartile range. Abbreviations used “C control”, “PD Parkinson’s disease”