Cerebrospinal fluid markers in Creutzfeldt-Jakob disease

Background: The objective was to assess the utility of total tau protein (tTau), the ratio of (tTau)/ 181 phosphorylated tau protein (P-Tau) and 14-3-3 protein, as diagnostic markers in cerebrospinal fluid (CSF) for Creutzfeldt-Jakob disease (CJD). Methods: CSF samples received from Norwegian hospitals between August 2005 and August 2007 were retrospectively selected from consecutive patients with tTau values > 1200 ng/ L (n = 38). The samples from patients clinically diagnosed with CJD (n = 12) were compared to those from patients with other degenerative neurological diseases: Alzheimer's/ vascular dementia (AD/ VaD, n = 21), other neurological diseases (OND, n = 5). Total Tau, P-Tau, and beta-Amyloid (A beta(42)) were measured with commercial kits. Additionally, 14-3-3 protein was measured semi-quantitatively by immunoblot. Results: The minimum cut-off limits for diagnosis of CJD were chosen from the test results. For tTau the lower limit was fixed at 3000 ng/ L, for the tTau/ P-Tau ratio it was 60, and for 14-3-3 protein it was 0.75 arbitrary units. For tTau and tTau/ P-Tau ratio, all but three CJD patients had levels above the minimum, whereas almost all of the other patients were below. For the 14-3-3 protein, two CJD patients were below the minimum and five were above. Only one of the other patients was higher than the limit. The sensitivities, specificities and diagnostic efficiencies were: tTau 75%, 92%, and 87%; tTau/ P-Tau 75%, 96%, and 89%; and 14-3-3 protein 80%, 96%, and 91%. Conclusion: The results suggest that 14-3-3 protein may be the better marker for CJD, tTau/ PTau ratio and tTau are also efficient markers, but showed slightly inferior diagnostic properties in this study, with tTau/ P-Tau marginally better than tTau.