Partial dissociation of PrPSc deposition and vacuolation in the brains of scrapie and BSE experimentally affected goats

The diagnosis of transmissible spongiform encephalopathies (TSEs) depends o n the detection of vacuolation in brain sections taken from affected indivi duals and/or the identification of the disease-associated isoform of the Pr P (prion) protein (PrPSc). During the course of an investigation, goats cli nically affected following experimental infection with three different sour ces of TSE (SSBP/1,CH1641 and BSE) developed widespread vacuolar degenerati on in the brain. With BSE, PrPSc was clearly recognized in affected goat br ain by immunocytochemistry (icc) and Western blotting, but in contrast the experimental scrapie sources SSBP/1 and CH1641 showed almost no or very lit tle PrPSc by icc. Western blot analysis of PrPSc from BSE-affected and SSBP /1-affected goat brain showed that the protein was present in brain affecte d by both TSE sources, but could not be used to determine how much protein was present. It became clear that PrPSc and vacuolation could be partially dissociated following challenge with two of the three TSE sources. Subtle d ifferences in glycosylation patterns between BSE- and SSBP/1-associated PrP protein isoforms could also be recognized, although these experimentally g enerated results should not be regarded as a BSE/scrapie differential test. However, our study warns that the reliance on PrPSc determination by ice a lone as a means by which to diagnose TSE infection may generate false negat ive results.