High diagnostic performance of plasma and cerebrospinal fluid beta-synuclein for sporadic Creutzfeldt-Jakob disease

Beta-synuclein is a promising cerebrospinal fluid and blood biomarker of synaptic damage. Here we analysed its accuracy in the discrimination between sporadic Creutzfeldt-Jakob disease (n = 150) and non-prion rapidly progressive dementias (n = 106). In cerebrospinal fluid, beta-synuclein performed better than protein 14-3-3 (AUC 0.95 vs. 0.89) and, to a lesser extent, than total tau (AUC 0.92). Further, the diagnostic value of plasma beta-synuclein (AUC 0.91) outperformed that of plasma tau (AUC 0.79) and neurofilament light chain protein (AUC 0.65) and was comparable to that of cerebrospinal fluid biomarkers. Beta-synuclein might represent the first highly accurate blood biomarker for the diagnosis of sporadic Creutzfeldt-Jakob disease.

Automated summary

Beta-synuclein is a promising biomarker for synaptic damage in cerebrospinal fluid and blood, and it can accurately distinguish sporadic Creutzfeldt-Jakob disease from non-prion rapidly progressive dementias. It outperforms protein 14-3-3 and total tau in cerebrospinal fluid, and has similar diagnostic value as cerebrospinal fluid biomarkers in plasma. Beta-synuclein may serve as the first highly accurate blood biomarker for the diagnosis of sporadic Creutzfeldt-Jakob disease.