Despite the high sensitivity and specificity of the 14-3-3 assays in humans and animals with transmissible spongiform encephalopathies (TSEs), it is not yet known how early in the course of these infections the proteins become detectable in the cerebrospinal fluid (CSF). Because (1) it has been established that pathological changes generally precede clinical signs, (2) and we 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 the proteins potentially may be diagnostic markers for subclinical infections during the asymptomatic incubation period. CSF has been collected from squirrel monkeys before and at monthly intervals following their inoculation with kuru, Creutzfeldt-Jakob disease, scrapie and bovine spongiform encephalopathy. DS-Page gel and Western immunoblotting analysis are presently being conducted.