We have continued to focus our research studies on the etiology, immunology, pathology, molecular biology, biochemistry, protein chemistry, and molecular genetics of subacute progressive degenerative diseases of the nervous system. Particular emphasis is placed on a group of rare diseases which we have identified as the transmissible spongiform encephalopathies (TSEs). This group consists of four human diseases--kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker diseases (GSS), and fatal familial insomnia (FFI); and five diseases of animals--scrapie, transmissible mink encephalopathy (TME), chronic wasting disease of deer and elk (CWD), feline spongiform encephalopathy (FSE) and bovine spongiform encephalopathy (BSE). We have demonstrated that these diseases are cerebral amyloidoses caused by posttranslational modification of a specific host precursor sialoglycoprotein resulting in the formation of amyloid fibrils. The normal cellular protein is on chromosome 20 in humans and 2 in mice and the abnormal isoform is formed de novo. The human diseases occur sporadically (80%), iatrogenically (2%) or as autosomal dominant genetic/infectious diseases (10%). By molecular genetic procedures 28 point mutations have been identified which significantly increases the probability of the conversion of the cellular protein to an infectious polypeptide. We continued to study the range and sensitivity of monoclonal or polyclonal anti-PrP antibodies against all known natural and experimental spongiform host ranges. Seven additional rabbit anti-PrP or PrP peptide antibodies were tested against PrPres of hamster, mouse, rat, sheep, goat, squirrel monkey, capuchin monkey, chimpanzees, human CJD, human GSS, human kuru and cervid chronic wasting disease. Two of these antibodies reacted very broadly and gave positive results with all of the antigens except PrPres from wasting disease in elk brain.
