Tubulovesicular particles occur early in the incubation period of murine scrapie

Tubulovesicular bodies are structures, apparently specific to the transmiss ible spongiform encephalopathies, which are of unknown composition and sign ificance. Prion protein (PrP) is absent from tubulovesicular bodies when ti ssues are examined by immunogold electron microscopy. In the F1 cross of C5 7 and VM mice (CVF1) infected with ME7 scrapie there is a marked degenerati on of hippocampal CA1 neurons. In this model the earliest changes seen, at about 100 days post inoculation (dpi) are a degeneration of axon terminals and synaptic loss. Terminal disease is around 250 dpi. In blind coded trial s we counted the number of tubulovesicular particles and estimated their de nsity in 56-76 electron micrographs taken from the stratum radiatum of each of one or two CVF1 ME7-infected mice at 84, 100, 126, 154 and 181 dpi and from four normal brain inoculated control mice. Tubulovesicular particles w ere present from 98 dpi and the density of particles increased with increas ing incubation period. The very early occurrence of tubulovesicular particl es, before the presence of significant pathology, argues that tubulovesicul ar particles are a part of the primary disease and are not epiphenomena.