Immunohistochemical detection of PrP in the medulla oblongata of sheep: the spectrum of staining in normal and scrapie-affected sheep

Sections of the medulla oblongata from the brains of sheep were examined fo r prion protein (PrP) by immunohistochemistry. On the basis of the morpholo gy and neuroanatomical distribution of the deposits, distinct disease-assoc iated patterns of PrP deposition were identified in scrapie-affected sheep, suggesting at least four distinct phenotypes of scrapie. In addition, clea rly defined patterns of PrP deposition, readily distinguished from the dise ase-associated PrP deposits, were identified in some normal sheep from scra pie-free flocks. In five sheep, believed to be preclinically affected by sc rapie, PrP deposition of a disease-specific type but of restricted distribu tion was identified, demonstrating the sensitivity of the technique for the diagnosis of scrapie. The neuroanatomical distribution of these early PrP deposits suggest that the route of entry of the scrapie agent into the brai n is via parasympathetic motor neurons in the vagus nerve which innervate t he gastrointestinal tract.