Cerebrospinal fluid markers in the differentiation of molecular subtypes of sporadic Creutzfeldt-Jakob disease

Eur J Neurol. 2016 Jun;23(6):1126-33. doi: 10.1111/ene.12991. Epub 2016 Mar 31.


Background and purpose: Cerebrospinal fluid (CSF) analysis supports the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) when applied within an adequate clinical context. A diagnostic potential has been attributed to CSF proteins such as 14-3-3, but also tau protein, phosphorylated tau (181P) (p-tau) protein, amyloid β1-42 , S100B and neuron-specific enolase (NSE). There has been only limited information available about the contribution of CSF analysis in the differentiation of various molecular sCJD subtypes.

Methods: The CSF levels of the aforementioned proteins from 73 sCJD patients with distinct molecular subtypes were determined.

Results: Differences in tau values were significant amongst the homozygous patients (MM and VV genotype) compared to the heterozygous group (P = 0.07 and P = 0.02 respectively). Significantly higher CSF tau levels (P = 0.003) and NSE (P = 0.02) but lower p-tau/tau ratio (P = 0.01) were observed in MM1 compared to MM2 patients. The p-tau/tau ratio enabled the differentiation of MV genotype with higher levels in PrP(sc) type 2 (P = 0.04). Elevation of S100B (P < 0.001) and NSE (P = 0.03) was observed in VV2 compared to VV1 subtype. PRNP codon 129 genotype, PrP(sc) isotype, disease duration and clinical stage influenced the test sensitivity in all proteins.

Conclusions: Cerebrospinal fluid protein levels might be useful in the pre-mortem differentiation of molecular sCJD subtypes when the codon 129 genotype is known.

Keywords: Creutzfeldt−Jakob disease; S100B; cerebrospinal fluid; neuron-specific enolase; tau.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / cerebrospinal fluid
  • Cell Differentiation
  • Creutzfeldt-Jakob Syndrome / cerebrospinal fluid
  • Creutzfeldt-Jakob Syndrome / diagnosis*
  • Creutzfeldt-Jakob Syndrome / genetics
  • Diagnosis, Differential
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Phosphopyruvate Hydratase / cerebrospinal fluid
  • Phosphorylation
  • Young Adult
  • tau Proteins / cerebrospinal fluid


  • Biomarkers
  • tau Proteins
  • Phosphopyruvate Hydratase