CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease

Neurology. 2006 Aug 22;67(4):637-43. doi: 10.1212/01.wnl.0000230159.67128.00.


Objectives: To analyze the diagnostic sensitivity and specificity of various brain-derived proteins (14-3-3, Tau, neuron specific enolase [NSE], and S100b) in the CSF of patients with Creutzfeldt-Jakob disease (CJD) and to analyze biologic factors that modify these parameters.

Methods: CSF was tested for 14-3-3, Tau, NSE, and S100b in 1,859 patients with sporadic, genetic, iatrogenic, and variant CJD, and in 1,117 controls.

Results: The highest sensitivity was achieved for 14-3-3 and Tau in sporadic CJD (85% and 86%), and a combined determination of 14-3-3 and Tau, S100b, or NSE increased the sensitivity to over 93%. A multivariate analysis showed that the sensitivity of all tests was highest in patients with the shortest disease duration, age at onset >40 years, and homozygosity at codon 129 of the prion protein gene. In a group of patients with repeated lumbar punctures, a second test also increased the diagnostic sensitivity.

Conclusions: The detection of elevated levels of brain-derived proteins in the CSF in patients with suspected Creutzfeldt-Jakob disease is a valuable diagnostic test. A second lumbar puncture may be of value in patients with atypical clinical course in whom the first test was negative.

Publication types

  • Controlled Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / cerebrospinal fluid*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / cerebrospinal fluid
  • Child
  • Child, Preschool
  • Creutzfeldt-Jakob Syndrome / cerebrospinal fluid*
  • Creutzfeldt-Jakob Syndrome / diagnosis*
  • Creutzfeldt-Jakob Syndrome / epidemiology
  • Diagnosis, Differential
  • Europe / epidemiology
  • Humans
  • Middle Aged
  • Nerve Tissue Proteins / cerebrospinal fluid*
  • Reproducibility of Results
  • Sensitivity and Specificity


  • 14-3-3 Proteins
  • Biomarkers
  • Nerve Tissue Proteins