Diagnostic value of 14-3-3β immunoblot and T-tau/P-tau ratio in clinically suspected Creutzfeldt-Jakob disease

Abstract

Creutzfeldt-Jakob disease (CJD) is a fatal prion disease characterized by rapid neurodegeneration. The clinical diagnosis is difficult and reliable diagnostic markers are highly desired. Here, we assess the sensitivity, specificity and predictive values of cerebrospinal fluid (CSF) tests for 14-3-3 protein and total tau (T-tau)/phospho-tau (P-tau) ratio among 36 patients with clinically suspected CJD. Nine of the 36 patients had CJD. These cases were all autopsy-proven. The 14-3-3 test was positive in 4 of the 9 CJD cases and falsely positive in 7 of the 27 patients with other diagnoses. The resulting figures for sensitivity, specificity, and positive and negative predictive values were 44%, 74%, 36% and 80%, respectively. The best result for distinguishing CJD from other diagnoses was obtained using a combined test for T-tau and T-tau/P-tau ratio and cut-off values of >1,400 pg/ml and >25, respectively. The resulting figures for sensitivity, specificity, and positive and negative predictive values were 78%, 93%, 78% and 93%, respectively. The achieved accuracy (89%) was significantly higher than that for the 14-3-3 test (67%; P=0.023). The high predictive values achieved by the combined tau test suggest that it could be used in conjunction with other diagnostic methods for accurate intra vitam diagnosis of CJD.