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

Abstract

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.

Figure 1

CSF and plasma beta‐syn levels in the diagnostic groups. (A) CSF and (B) plasma beta‐syn values in sporadic Creutzfeldt–Jakob disease and non‐prion RPD; (C) CSF and (D) plasma beta‐syn levels in sporadic Creutzfeldt–Jakob disease most prevalent molecular subtypes [MM(V)1, VV2, and MV2K]. β‐syn values are presented as log(pg/mL); median, and interquartile range are shown for the biomarker levels. p values of Mann–Whitney or Dunn's post hoc test after Kruskal–Wallis test are reported. CSF, cerebrospinal fluid; RPD, rapidly progressive dementia; sCJD, sporadic Creutzfeldt–Jakob disease.