title: A prospective study of CSF markers in 250 patients with possible Creutzfeldt-Jakob disease.
abstract: OBJECTIVE
  To investigate various cerebrospinal fluid (CSF) markers that could assist in the clinical diagnosis of Creutzfeldt-Jakob disease (CJD).
  
  
  METHODS
  CSF samples were analysed for the presence of 14-3-3 protein, microtubule associated protein tau, and beta amyloid in 250 patients with possible CJD. Densitometric analysis was used to quantify the level of 14-3-3 in all patients.
  
  
  RESULTS
  Analysis of the clinical data showed that cerebellar signs or myoclonus combined with progressive dementia were the main features leading to a clinical suspicion of CJD. While 14-3-3 detection had a sensitivity of 100% and a specificity of 92%, tau determination using a threshold of 1300 pg/ml had a sensitivity of 87% and a specificity of 97%. If the protocol for the analysis of 14-3-3 was modified (using densitometric analysis) a higher specificity (97%) could be obtained, but with a lower sensitivity (96%). Maximum sensitivity, specificity, and positive predictive value were obtained with a combination of 14-3-3 and beta amyloid determinations. The concentrations of 14-3-3 and tau in the CSF were reduced in CJD patients with a long duration of disease (more than one year; p < 0.05). The concentrations of 14-3-3 or tau were lowest at the onset or at the end stage of the disease, while the beta amyloid concentration remained low throughout the course of the disease.
  
  
  CONCLUSIONS
  Both 14-3-3 and tau protein are sensitive and specific biomarkers for CJD. The combination of 14-3-3 and beta amyloid analysis resulted in the maximum sensitivity, specificity, and positive predictive value. When these biomarkers are used in the diagnosis of CJD, the phase of the disease in which the CSF sample was obtained should be taken into account. Disease duration, dependent on the PrP genotype, also has a significant influence on the level of 14-3-3 and tau in the CSF.
authors.affiliation: Born Bunge Foundation, University of Antwerp, Wilrijk, Belgium. Institute of Public Health Louis Pasteur, Brussels, Belgium. bartve@uia.ua.ac.be
authors.forename: B
authors.initials: B
authors.lastname: Van Everbroeck
authors.forename: S
authors.initials: S
authors.lastname: Quoilin
authors.forename: J
authors.initials: J
authors.lastname: Boons
authors.forename: J J
authors.initials: JJ
authors.lastname: Martin
authors.forename: P
authors.initials: P
authors.lastname: Cras
mesh_terms: D048948:14-3-3 Proteins; D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D014446:Tyrosine 3-Monooxygenase / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D048948:14-3-3 Proteins; D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins; D014446:Tyrosine 3-Monooxygenase