Onset and distribution of tissue PrP accumulation in scrapie-affected suffolk sheep as demonstrated by sequential necropsies and tonsillar biopsies

Tonsillar biopsies (single or multiple) or necropsies, or both, were performed on sheep taken from a Suffolk flock in which frequent cases of scrapie had occurred over a period of several years. Clinically affected sheep of the susceptible PrPAQ/AQ genotype had widespread disease-specific PrP accumulation in the central nervous system (CNS). lymphoreticular system and peripheral ganglia. In nine healthy PrPAQ/AQ Suffolk sheep between 4 and 7 years of age, PrP could not be demonstrated post mortem in any of the lymphoreticular tissues, or in the peripheral ganglia or CNS. Tonsillar biopsies taken from animals of the resistant PrPAR/AR and PrPAR/AQ genotypes at age 3, 8, 14, 20 or 26 months did not show PrP accumulation. Disease-specific PrP accumulation in tonsillar biopsies from PrPAQ/AQ sheep was not seen in 20 animals aged 3 months, but was found in two of 10 animals at age 8 months and in eight of 10 animals at age 20 months. The numbers of PrP-positive tonsillar biopsies obtained from sheep previously biopsied on more than one occasion was greater than the number of positive tonsils obtained from other susceptible sheep of comparable ages. The earliest disease-specific PrP accumulation seen was in tangible body macrophases within germinal centres and only later was it detected in cells resembling follicular dendritic cells. Fourteen PrPAQ/AQ sheep examined post mortem at up to 17 months of age and which had not previously been biopsied or were biopsied only once had no CNS or tonsillar PrP accumulations. Two of these sheep subjected to necropsy at 14 months had PrP accumulation in lymphoreticular tissue, where it was confined to the mesenteric lymphnodes. In susceptible sheep, only low levels of immunohistochemically detectable PrP were present in a minority of follicles from tonsillar biopsies of young lambs, but by 14 months of age widespread PrP accumulation, affecting many or even all follicles, was present. Although clinical cases had widespread PrP accumulations in viscera, susceptible survivors had no such accumulations in tissues of the lymphoreticular system, peripheral nervous system or CNS, suggesting that some animals were not exposed to infection or were exposed to a non-infectious dose.