14-3-3 protein levels and isoform patterns in the cerebrospinal fluid of Creutzfeldt-Jakob disease patients in the progressive and terminal stages.

To elucidate the diagnostic value and to establish the 14-3-3 isoform patterns in the cerebrospinal fluid (CSF) of Creutzfeldt-Jakob disease (CJD) patients, we analysed the 14-3-3 isoform patterns in the CSF of 11 CJD patients using the Western immunoassay technique. 14-3-3 protein was detected in the CSF of seven CJD patients in the progressive stage, but not in four patients in the terminal stages whose brains were severely atrophied. The amount of 14-3-3 protein measured semi-quantitatively in the CSF was correlated with that of neuron-specific enolase measured using an enzyme-linked immunosorbent assay in the same CSF. CJD patients showed five dominant 14-3-3 isoforms, gamma, epsilon, zeta, eta and beta, but 14-3-3 tau, which mainly originates from T lymphocytes, was not detected. 14-3-3 protein is released into the CSF as a consequence of the extensive and rapid destruction of the brain, and the presence of the five isoforms enhances the diagnostic value of 14-3-3 protein in the progressive stage.