β-synuclein in cerebrospinal fluid as a potential biomarker for distinguishing human prion diseases from Alzheimer's and Parkinson's disease.

Abstract

Background: β-synuclein (β-syn), mainly expressed in central nerve system, is one of the biomarkers in cerebrospinal fluid (CSF) and blood for synaptic damage, which has been reported to be elevated in CSF and blood of the patients of prion diseases (PrDs).

Methods: We analyzed 314 CSF samples from patients in China National Surveillance for CJD. The diagnostic groups of the 223 patients with PrDs included sporadic Creutzfeldt-Jacob disease (sCJD), genetic CJD (gCJD), fatal familial insomnia (FFI) and Gerstmann-Straussler-Scheinker (GSS). 91 patients with non-PrDs comprised Alzheimer's disease (AD), Parkinson's disease (PD), viral encephalitis (VE) or autoimmune encephalitis (AE) were enrolled in the control groups. The CSF β-syn levels were measured by a commercial microfluidic ELISA. The Mann-Whitney U test and Kruskal-Wallis H test were employed to analyze two or more sets of continuous variables. Multiple linear regression was also performed to evaluate the factors for CSF β-syn levels. Receiver operating characteristics (ROC) curves and area under the curve (AUC) values were used to assess the diagnostic performance of β-syn.

Results: The median of β-syn levels (2074 pg/ml; IQR: 691 to 4332) of all PrDs was significantly higher than that of non-PrDs group (504 pg/ml; IQR: 126 to 3374). The CSF β-syn values in the cohorts of sCJD, T188K-gCJD, E200K-gCJD and P102L-GSS were remarkably higher than that of the group of AD + PD, but similar as that of the group of VE + AE. The elevated CSF β-syn in sCJD and gCJD cases was statistically associated with CSF 14-3-3 positive and appearance of mutism. ROC curve analysis identified satisfied performance for distinguishing from AD + PD, with high AUC values in sCJD (0.7640), T188K-gCJD (0.8489), E200K-gCJD (0.8548), P102L-GSS (0.7689) and D178N-FFI (0.7210), respectively.

Conclusion: Our data here indicate that CSF β-syn is a potential biomarker for distinguishing PrDs (gCJD, sCJD and GSS) from AD and PD, but is much less efficient from VE and AE. These findings have critical implications for early diagnosis and monitoring of synaptic integrity in prion diseases.