During the past two years, more than 1,000 cases of a neurological disorder of cattle, bovine spongiform encephalopathy (BSE), have been confirmed from farms throughout Great Britain. The neurological signs and brain pathology of BSE resemble those produced in other species by the pathogens of scrapie and related disorders. The discovery of fibrils similar to scrapie-associated fibrils in detergent extracts o BSE-affected brain supported the clinical and pathological diagnosis of the disease, but has been controversial. Scrapie-associated fibrils are found in brain extracts of all species affected by scrapie and diseases caused by related pathogens. They are pathological aggregates of a neuronal membrane protein termed PrP and a protease-resistant form of PrP is a molecular marker of scrapie-associated fibrils. In this report, we show the major protein of BSE fibrils is the bovine homologue of PrP as judged by its size, protease resistance, immunoreactivity, lectin binding and partial N-terminal protein sequence. This confirms that BSE is a scrapie-like disease.

Scrapie‐associated fibrils (SAF) are disease‐specific structures found in extracts of the brains of animals affected with scrapie. These structures are pathological aggregates of a normal host protein (PrP). Abnormal post‐translational modification of PrP has been suggested to explain its aberrant properties in scrapie‐affected brains and although there is a form of PrP in SAF indistinguishable in size from the protein in uninfected brain, lower‐molecular‐mass variants of PrP are also found in SAF fractions. We report the characterisation of the multiple forms of PrP found in SAF fractions purified from mouse brain affected by the ME7 strain of scrapie. The quantitively major forms of PrP in SAF prepared without the use of proteinase K have the amino‐terminal sequence Lys‐Lys‐Arg‐Pro‐Lys‐Pro‐Gly‐Gly‐, identical to that predicted for the amino‐terminus of normal mouse brain PrP. However N‐terminal cleavage of some PrP does occur in vivo within a domain of repetitive sequences at sites similar to but distinct from those cut by proteinase K in vitro. This suggests the conformation of the protein in aggregates in vivo does not differ extensively from that in detergent‐treated SAF in vitro. We conclude that the size diversity of PrP in SAF is only partly due to N‐terminal proteolysis and is independent of the proteolysis that occurs if proteinase K is used in the purification of SAF. Apart from proteolytic changes in the structure of PrP, we found a novel, as yet unidentified, amino‐acid derivative of the arginine residue at position 3 in mouse PrP, which may predispose PrP to form SAF.

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