Prion protein immunocytochemistry helps to establish the true incidence of prion diseases.

Creutzfeldt-Jakob disease (CJD) and Gerstmann-Strüssler-Scheinker disease (GSSD) are transmissible spongiform encephalopathies or prion diseases affecting man. It has been reported that prion diseases may occur without the histological hallmarks of spongiform encephalopathies: vacuolation of the cerebral grey matter, neuronal loss and astrocytosis. These cases without characteristic neuropathology may go undiagnosed and consequently the true incidence of transmissible dementias is likely to have been under-estimated. Immunocytochemistry using antibodies to prion protein gives positive staining of these cases, albeit the pattern of immunostaining differs from that seen in typical forms. Accumulation of prion protein is a molecular hallmark of prion diseases, and thus a reproducible, speedy and cost-efficient immunocytochemical screening of unusual dementias may help to establish the true incidence of prion diseases.

Unaltered susceptibility to BSE in transgenic mice expressing human prion protein.

Prion diseases are transmissible neurodegenerative conditions of humans and animals. Prions consist principally of a post-translationally modified form of prion protein (PrP), PrP(Sc), which is partly protease resistant. Transmission of prion diseases between species is limited by a 'species barrier' determined in part by the degree of sequence homology between host PrP and inoculated PrP(Sc) (ref.3) and by prion strain type. The epidemic of bovine spongiform encephalopathy (BSE) in the United Kingdom and other countries has led to concerns that transmission to humans may occur by dietary exposure. BSE appears to be caused by a single strain, distinct from those of natural or experimental scrapie, which is also seen in the new prion diseases of cats and ruminants that have presumably arisen from dietary BSE exposure. Here we show that transgenic mice expressing human PrP in addition to mouse PrP can generate human PrP(Sc) and 'human' prions. These mice therefore provide a model to study experimentally the species barrier limiting BSE transmission to humans. Incubation periods to BSE in transgenic mice are not shortened by expression of human PrP, and only mouse PrP(Sc) is produced in response to such challenge.