Effects of agent strain and host genotype on PrP accumulation in the brain of sheep naturally and experimentally affected with scrapie

Different cellular and neuroanatomical types of disease-specific prion protein (PrPd) accumulation in the brain were identified in sheep of different breeds and PrP genotypes exposed to experimental or natural scrapie infection. Immunohistochemical examination of the brains of 43 sheep with clinical signs compatible with scrapie revealed 12 different PrPd types, which were subjectively quantified in eight different brain regions. The PrPd types were grouped into four PrPd patterns, the relative magnitude of which provided the PrPd profile of each sheep examined. The analysis of the differences in magnitude and relative proportion of each of these PrPd types and patterns indicated (1) an effect of the scrapie strain on the PrPd profile, and (2) a possible effect of the host genotype on the magnitude of PrPd accumulation in the brain, apparently related to the incubation period. Furthermore, intraneuronal deposition of PrPd was the type most closely associated with the development of clinical disease. We conclude that different scrapie strains can be distinguished by PrP immunohistochemical examination of brains of affected animals. (C) 2002 Harcourt Publishers Ltd.