title: Use of 14-3-3 and other brain-specific proteins in CSF in the diagnosis of variant Creutzfeldt-Jakob disease.
abstract: OBJECTIVE
  The detection of the protein 14-3-3 in the CSF has been shown to be a reliable and sensitive marker for sporadic Creutzfeldt-Jakob disease (CJD). Other brain-specific proteins such as neuron specific enolase (NSE), S-100b, and tau protein have also been reported to be increased in the CSF of patients with sporadic CJD. In 1996 a variant of CJD (vCJD) was described which is likely to be causally linked to the bovine spongiform encephalopathy agent. This study reports and compares the findings of CSF brain specific protein analysis in 45 patients with vCJD and in 34 control patients.
  
  
  METHODS
  The CSF from 45 patients with vCJD and 34 controls were investigated for the presence of 14-3-3 by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting with chemiluminescent detection. Tau protein, S-100b, and NSE concentrations in CSF were measured using enzyme immunoassays.
  
  
  RESULTS
  Protein 14-3-3 was detected in the CSF of 22/45 patients with vCJD and in 3/34 controls. The mean concentrations of NSE, S-100b, and tau protein in CSF were significantly raised in patients with vCJD compared with controls. The positive predictive value of CSF 14-3-3 was 86% and the negative predictive value was 63%. These values are lower than those reported for sporadic CJD. An increased CSF tau had a positive predictive value of 93% and a negative predictive value of 81%. The combination of CSF 14-3-3 and/or increased CSF tau had a positive predictive value of 91% and a negative predictive value of 84%.
  
  
  CONCLUSIONS
  CSF protein 14-3-3 is not as useful a marker for vCJD as it is for sporadic CJD. Increased concentration of CSF tau was found to be a sensitive marker of vCJD but as concentrations may be increased in many forms of non-CJD dementia, this may limit its usefulness as a diagnostic test.
authors.affiliation: The National Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. Alison.Green@ed.ac.uk
authors.forename: A J
authors.initials: AJ
authors.lastname: Green
authors.forename: E J
authors.initials: EJ
authors.lastname: Thompson
authors.forename: G E
authors.initials: GE
authors.lastname: Stewart
authors.forename: M
authors.initials: M
authors.lastname: Zeidler
authors.forename: J M
authors.initials: JM
authors.lastname: McKenzie
authors.forename: M A
authors.initials: MA
authors.lastname: MacLeod
authors.forename: J W
authors.initials: JW
authors.lastname: Ironside
authors.forename: R G
authors.initials: RG
authors.lastname: Will
authors.forename: R S
authors.initials: RS
authors.lastname: Knight
mesh_terms: D048948:14-3-3 Proteins; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D007562:Creutzfeldt-Jakob Syndrome / Q000134:cerebrospinal fluid*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid*; D011237:Predictive Value of Tests; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000134:cerebrospinal fluid*; D012680:Sensitivity and Specificity; D014446:Tyrosine 3-Monooxygenase / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D048948:14-3-3 Proteins; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D016875:tau Proteins; D014446:Tyrosine 3-Monooxygenase; D010751:Phosphopyruvate Hydratase