Proteome Analysis of Potential Synaptic Vesicle Cycle Biomarkers in the Cerebrospinal Fluid of Patients with Sporadic Creutzfeldt-Jakob Disease.

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most frequent fatal human prion disease with a rapid progression and unknown mechanism. The synaptic vesicle (SV) cycle pathway has been a hot research field associated with many neurodegenerative diseases that affect synaptic function and thus may affect pathogenesis of the disorder. Here, we used the iTRAQ-based proteomic method and a KEGG pathway enrichment analysis to meticulously analyze all pathways involved in sCJD disease. In total, 1670 proteins were validated in pooled cerebrospinal fluid (CSF) from 20 patients with sCJD compared with that from 13 patients without CJD. The demographic analysis demonstrated that 557 proteins were upregulated and 595 proteins were downregulated with a 1.5-fold change, and 690 proteins involved in 39 pathways changed significantly (p ≤ 0.05) according to the enrichment analysis. The SV cycle pathway and proteins involved were further evaluated, and 14 proteins were confirmed to participate in the SV cycle pathway due to increased expression. Six key proteins, such as AP2A1, SYT1, SNAP25, STXBP1, CLTB, and Rab3a, showed the same trend by western blot as detected by iTRAQ. This is the first study to use high-throughput proteomics to accurately identify and quantify proteins in the SV cycle pathway of a neurodegenerative disease. These results will help define the mechanism and provide new insight into the pathogenetic factors involved in the SV cycle pathway in patients with sCJD. We hope that promising biomarkers can be identified in the CSF of patients with sCJD and other neurodegenerative disorders to help predict disease progression.