Isoform pattern of 14-3-3 proteins in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease

Two-dimensional polyacrylamide gel electrophoresis of CSF has been used in the diagnosis of Creutzfeldt-Jakob disease (CJD). One of the two diagnostic protein spots was identified as isoform(s) of the 14-3-3 family of abundan t brain proteins. This has led to the development of one-dimensional 14-3-3 sodium dodecyl sulfate polyacrylamide gel electrophoresis immunoblot, whic h is currently used to support the diagnosis of CJD. In the present study e mploying western blot analysis, we have identified the panel of 14-3-3 isof orms that appear in the CSF of 10 patients with CJD compared with 10 patien ts with other dementias. The results clearly show that the 14-3-3 isoforms beta, gamma, epsilon, and eta are present in the CSF of patients with CJD a nd can be used to differentiate other dementias. 14-3-3 eta also gave a bas eline signal in all patients with other dementias, including six patients w ith Alzheimer's disease. The presence of 14-3-3 eta in the CSF of a patient with herpes simplex encephalitis was particularly noteworthy. This study h as determined that isoform-specific 14-3-3 antibodies against beta, gamma, and epsilon should be considered for the neurochemical differentiation of C JD from other neurodegenerative diseases.