Creutzfeldt-Jakob disease: diagnostic utility of 14-3-3 protein immunodetection in cerebrospinal fluid

With the aim of improving the pre-mortem diagnostic accuracy of sporadic Cr eutzfeldt-Jakob disease (CJD), there has been considerable recent interest in the merit of immunodetecting 14-3-3 proteins in the cerebrospinal fluid (CSF) using Western blotting, with cumulative support for the utility of th is technique. As a corollary, during a 20 month period, CSF samples from an unselected prospective series of 124 patients in whom sporadic CJD was a d ifferential diagnostic possibility were examined by the Australian Creutzfe ldt-Jakob disease Registry (ACJDR) for the presence of 14-3-3 proteins. Fol low up to achieve a final diagnosis or clinical outcome was successful in 1 19. For definite and probable sporadic CJD combined, a positive result was 91.4% sensitive, while the sensitivity for the pathologically verified grou p alone was 96.0%, A negative outcome was 92.5% specific with false positiv e results seen in Rye patients with diagnoses which included inflammatory C NS disorders, cerebral ischaemia and dementia with Lewy bodies (DLB). Immun odetectable 14-3-3 proteins were present in three of four symptomatic patie nts with prion protein gene (PRNP) mutations. CSF samples containing signif icant amounts of blood were confirmed as suboptimal, with weak or qualitati vely unusual positive results found in greater than 50% of such specimens, with only one of 14 such cases ultimately classified as definite or probabl e CJD. (C) 2000 Harcourt Publishers.