Validation of α-Synuclein as a CSF Biomarker for Sporadic Creutzfeldt-Jakob Disease

Mol Neurobiol. 2018 Mar;55(3):2249-2257. doi: 10.1007/s12035-017-0479-5. Epub 2017 Mar 21.


The analysis of cerebrospinal fluid (CSF) biomarkers gains importance in the differential diagnosis of prion diseases. However, no single diagnostic tool or combination of them can unequivocally confirm prion disease diagnosis. Electrochemiluminescence (ECL)-based immunoassays have demonstrated to achieve high diagnostic accuracy in a variety of sample types due to their high sensitivity and dynamic range. Quantification of CSF α-synuclein (a-syn) by an in-house ECL-based ELISA assay has been recently reported as an excellent approach for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), the most prevalent form of human prion disease. In the present study, we validated a commercially available ECL-based a-syn ELISA platform as a diagnostic test for correct classification of sCJD cases. CSF a-syn was analysed in 203 sCJD cases with definite diagnosis and in 445 non-CJD cases. We investigated reproducibility and stability of CSF a-syn and made recommendations for its analysis in the sCJD diagnostic workup. A sensitivity of 98% and a specificity of 97% were achieved when using an optimal cut-off of 820 pg/mL a-syn. Moreover, we were able to show a negative correlation between a-syn levels and disease duration suggesting that CSF a-syn may be a good prognostic marker for sCJD patients. The present study validates the use of a-syn as a CSF biomarker of sCJD and establishes the clinical and pre-analytical parameters for its use in differential diagnosis in clinical routine. Additionally, the current test presents some advantages compared to other diagnostic approaches: it is fast, economic, requires minimal amount of CSF and a-syn levels are stable along disease progression.

Keywords: Biomarkers; Cerebrospinal fluid; ELISA; Electrochemiluminescence; Sporadic Creutzfeldt-Jakob; α-Synuclein.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Aged
  • Biomarkers / cerebrospinal fluid
  • Cohort Studies
  • Creutzfeldt-Jakob Syndrome / cerebrospinal fluid*
  • Creutzfeldt-Jakob Syndrome / diagnosis*
  • Female
  • Humans
  • Male
  • Middle Aged
  • alpha-Synuclein / cerebrospinal fluid*


  • Biomarkers
  • alpha-Synuclein

Supplementary concepts

  • Creutzfeldt-Jakob Disease, Sporadic