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.

Cerebrospinal Fluid Levels of Neurogranin in Parkinsonian Disorders

“…Furthermore, increased Ng has been linked to cognitive decline and conversion from MCI to AD . In this study focusing on parkinsonian disorders, confirming some studies but contradicting others, we find decreased levels of Ng in PD compared to controls. We also found decreased levels of Ng in MSA and PSP using both assays and in PDD using Ng‐EI.…”

“…Contradicting one study, but supporting another, we found no association between levels of Ng and motor dysfunction . Furthermore, supporting results from one study, we found no associations between Ng and cognitive impairment in parkinsonian disorders.…”

“…Few studies have examined CSF Ng in PD, finding unchanged or decreased levels of Ng compared to controls . Even scarcer are studies on Ng and cognitive decline or motor dysfunction, and results are conflicting . In PSP, MSA, corticobasal syndrome (CBS), and DLB/PDD, Ng has been found to be unchanged compared to controls and lower compared to AD .…”

Cognitive decline in Parkinson disease

“…These findings suggest that cortical synaptic changes lead to cognitive decline in PD, consistent with imaging findings (see below), and preliminary work indicates that synaptic changes are also reflected in the cerebrospinal fluid (CSF). Neurogranin levels were found to be increased in the CSF in AD 33 , probably due to increased intracellular sequestration, and similar findings have been reported — and linked with cognitive decline — in PD 34 . Thus, CSF levels of synaptic proteins are potential biomarkers of future cognitive decline.…”

A Lewy-testes demencia klinikai és neuropatológiai jellemzői

“…A posztszinaptikus neurogranin fehérje vizsgálata a liquorban nem hozott meggyőző eredményt. Noha AD-ben és PD-ben is emelkedett szintet mértek az egészséges csoporthoz képest, a DLB-ben mért szint nem képes biztosan különbséget tenni sem a kontrollcsoporttól, sem az egyéb, demenciával járó betegségek-től [66]. A kiterjedt vizsgálatok ellenére eddig nem sikerült olyan liquor-biomarkert azonosítani, amelyik specifikus lenne DLB-re és biztonsággal el tudná azt kü-löníteni más neurodegeneratív kórképektől.…”