Tau protein and 14-3-3 protein in the differential diagnosis of Creutzfeldt-Jakob disease

Neurology. 2002 Jan 22;58(2):192-7. doi: 10.1212/wnl.58.2.192.


Background: Diagnosis of Creutzfeldt-Jakob disease (CJD) is made according to the typical clinical picture and can be supported by a positive 14-3-3 CSF immunoblot. Promising results for the diagnostic sensitivity and specificity of tau-protein measurement in CSF already have been described in a smaller group of patients. Both tests in a larger group of patients with the differential diagnosis of CJD were evaluated.

Methods: CSF of 297 patients under the differential diagnosis of CJD (109 definite, 55 probable, 39 possible; 85 others, 1 iatrogenic, 8 genetic), 23 nondemented control subjects, and 15 non-CJD patients with positive 14-3-3 immunoblots were analyzed. The 14-3-3 immunoblot bands were semiquantitatively rated as strong, medium, and weak. Tau-protein was analyzed using a commercially available ELISA. In addition, patients were neuropathologically classified according to prion protein type and polymorphism at codon 129.

Results: A diagnostic sensitivity of 94%, a diagnostic specificity of 90%, and a positive predictive value of 92% were achieved for tau-protein at a cut-off of 1,300 pg/mL. These results are comparable with those of the 14-3-3 immunoblot. For patients with type II prion protein and methionine/valine or valine/valine polymorphism at codon 129, tau-protein has a higher diagnostic sensitivity than 14-3-3 protein. Tau-protein levels were significantly higher in patients with higher-rated 14-3-3 immunoblot bands.

Conclusion: The differential diagnostic significance of the 14-3-3 immunoblot is similar to that of the tau-protein ELISA. The advantage of the tau-protein ELISA is that it is easy to use in routine laboratories. Patients with a negative 14-3-3 immunoblot already have measurable tau-protein levels. This increases information on 14-3-3-negative patients with CJD and especially on patients with other diseases.

Publication types

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

MeSH terms

  • 14-3-3 Proteins
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Creutzfeldt-Jakob Syndrome / cerebrospinal fluid
  • Creutzfeldt-Jakob Syndrome / diagnosis*
  • Creutzfeldt-Jakob Syndrome / genetics
  • Creutzfeldt-Jakob Syndrome / physiopathology
  • Dementia / etiology
  • Dementia / physiopathology
  • Diagnosis, Differential
  • Enzyme Inhibitors / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoblotting
  • Male
  • Middle Aged
  • Sensitivity and Specificity
  • Tyrosine 3-Monooxygenase / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid*


  • 14-3-3 Proteins
  • Enzyme Inhibitors
  • tau Proteins
  • Tyrosine 3-Monooxygenase