The Western immunoblot for the detection of 14-3-3 protein in the cerebrospinal fluid of human patients with sporadic or familial spongiform encephalopathy and chimpanzees with experimentally induced TSEs has provided for a highly sensitive and specific test in support of a clinical diagnosis of these diseases. However, it is not known how early in the course of these infections the protein becomes detectable in the CSF. We have demonstrated in spider monkeys that neuropathological lesions precede clinical signs and have hypothesized that 14-3-3 proteins are detectable due to neuronal loss at a rate sufficient to outpace the normal turnover and resorption of CSF. We have detected these proteins in the CSF of chimpanzees inoculated with CJD several weeks before clinical signs become recognizable. In humans with very early behavorial changes the test has been negative but repeat collections as the disease progresses the test becomes positive. To more definitively determine the earliest possible detection of 14-3-3 proteins in CSF we have inoculated ten chimpanzees with sporadic, iatrogenic and familial strains of CJD and are colelcting CSF and blood at intervals of every six weeks. Concurrently we have determined the stablility of 14-3-3 protein and have shown that the protein in CSF is stable at room temperature and 4C for over 35 days and indefinitely at 20C.
