Introduction to scrapie and perspectives on current scrapie research

Scrapie is the prototype of a family of six transmissible diseases which includes Creutzfeldt-Jakob disease, the only known transmissible human dementia. Bovine spongiform encephalopathy is the most recent addition to the family. Alzheimer's disease is not known to be transmissible. However the pathogenesis of both scrapie and Alzheimer's disease is associated with the modification of (different) normal brain proteins to form various types of amyloid. In scrapie, the evidence suggests that a membrane glycoprotein, PrP, is the precursor of the scrapie associated fibrils (SAF) found in brain extracts, and also of the extracellular deposits of cerebral amyloid which resemble the Alzheimer plaque cores. The host gene that makes PrP is closely linked to the gene Sinc which controls the incubation period of the many different scrapie strains in mice. It is possible that these two genes are the same, i.e., that PrP is the product of Sinc gene. In addition, scrapie infectivity copurifies with modified PrP (SAF). Modified PrP may be the protective protein coat of the independent scrapie genome which some think is a very small nucleic acid. Others believe that the amyloidogenic form of PrP is itself the infectious scrapie agent. Whatever the true situation, there appear to be very short pathways between scrapie infection and amyloidogenesis.