Use of 14-3-3 and other brain-specific proteins in CSF in the diagnosis ofvariant Creutzfeldt-Jakob disease

Objectives - 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 diseas e (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 C SF of patients with sporadic CJD. In 1996 a variant of CJD (vCJD) was descr ibed which is likely to be causally Linked to the bovine spongiform encepha lopathy agent. This study reports and compares the findings of CSF brain sp ecific protein analysis in 45 patients with vCJD and in 34 control patients . Methods - The CSF from 45 patients with vCJD and 34 controls were investiga ted for the presence of 14-3-3 by SDS-polyacrylamide gel electrophoresis (S DS-PAGE) and western blotting with chemiluminescent detection. Tau protein, S-100b, and NSE concentrations in CSF were measured using enzyme immunoass ays. Results - Protein 14-3-3 was detected in the CSF of 22/45 patients with vCJ D and in 3/34 controls. The mean concentrations of NSE, S-100b, and tau pro tein in CSF were significantly raised in patients with vCJD compared with c ontrols. The positive predictive value of CSF 14-3-3 was 86% and the negati ve 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/o r increased CSF tau had a positive predictive value of 91% and a negative p redictive value of 84%. Conclusions - CSF protein 14-3-3 is not as useful a marker for vCJD as it i s for sporadic CJD. Increased concentration of CSF tau was found to be a se nsitive 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.