Pathology of nonhuman spongiform encephalopathies: variations and their implications for pathogenesis

Microscopic cavitation of the central nervous system (CNS) is a variable, non-specific feature of several different diseases of animals. In none, however, has it received more discussion than in scrapie, a naturally occurring disease of sheep, the clinical signs of which have been known for at least two centuries; yet consensus on the essential neurodegenerative pathology of scrapie emerged only three decades ago. The subsequent recognition of such changes in other species, including man, was a crucial factor in establishing the unifying concept of the transmissible spongiform encephalopathies (TSE). Recently these disorders have been recorded in several additional species, most significantly in domestic cattle as a foodborne epidemic. Although the TSE of animals present as infections, their pathology is confined to the CNS and has more in common with neuronal system degenerations with selective, usually symmetrical and progressive lesions, unaccompanied by inflammation. In a given host species the distribution of lesions may show variation, as in sheep scrapie or uniformity, as in bovine spongiform encephalopathy. Vacuolar or spongiform change is the most useful feature in routine diagnosis, in spite of variability in its prominence. The molecular pathology of the TSE is characterised by an abnormal isoform of a host-encoded membrane protein, the prion protein (PrP), accumulation of which is specially related to vacuolar change. There remain considerable deficits in our knowledge of the pathogenesis of the naturally occurring animal TSE, not least the extraneural events leading to CNS involvement and the relative roles of vacuolar change and PrP accumulation.