Strain-associated variations in abnormal PrP trafficking of sheep scrapie.

Prion diseases are associated with the accumulation of an abnormal form of the host-coded prion protein (PrP). It is postulated that different tertiary or quaternary structures of infectious PrP provide the information necessary to code for strain properties. We show here that different light microscopic types of abnormal PrP (PrP(d)) accumulation found in each of 10 sheep scrapie cases correspond ultrastructurally with abnormal endocytosis, increased endo-lysosomes, microfolding of plasma membranes, extracellular PrP(d) release and intercellular PrP(d) transfer of neurons and/or glia.

Scrapie-specific neuronal lesions are independent of neuronal PrP expression.

In the transmissible spongiform encephalopathies (TSE), accumulation of the abnormal disease-specific prion protein is associated with neurodegeneration. Previous data suggested that abnormal prion protein (PrP) could induce neuronal pathology only when neurons expressed the normal form of PrP, but conflicting evidence also has been reported. Understanding whether neuronal PrP expression is required for TSE neuropathological damage in vivo is essential for determining the mechanism of TSE pathogenesis.

Relationships between ultrastructural scrapie pathology and patterns of abnormal prion protein accumulation.

On immunohistochemical examination several morphological types of disease-specific prion protein (PrP(d)) accumulation are recognised in the brain of sheep suffering from scrapie. The present study examined the relationship between the type of PrP(d) deposits seen by light microscopy and ultrastructural changes in the olivary nuclei and the dorsal motor nucleus of the vagus (DMNV) in naturally infected sheep with clinical scrapie. The nature and magnitude of sub-cellular morphological changes found in the olivary nuclei differed from the patterns of degeneration previously described in the DMNV.