Increased Immunohistochemical Labelling for Prion Protein Occurs in Diverse Neurological Disorders of Sheep: Relevance for Normal Cellular PrP Function

SummaryThe classical prion diseases (e.g. scrapie of sheep and goats and bovine spongiform encephalopathy of cattle) are characterized by the accumulation of abnormal forms of the prion protein (PrP), usually recognized by their relative resistance to proteolysis compared with the physiological cellular forms of PrP. However, novel prion diseases have been detected in sheep, cattle and man, in which the abnormal PrP has less resistance to proteolysis than identified previously. These more subtle differences between abnormal and normal forms of PrP can be problematic in routine diagnostic tests and raise questions in respect of the range of PrP disorders. Abnormal accumulations of PrP in atypical and classical prion diseases can be recognized by immunohistochemistry. To determine whether altered PrP expression or trafficking might occur in nosological entities not previously connected with prion disease, the brains of sheep affected with diverse neurological conditions were examined for evidence of altered PrP labelling. Such altered immunolabelling was detected in association with either basic lesions or specific diseases. Some reactive glial cells and degenerate neurons found in several different recognized disorders and non-specific inflammatory processes were associated with abnormal PrP labelling, which was absent from brains of healthy, age-matched sheep. The results agree with previous indications that normal PrP function may be linked with the oxidative stress response, but the data also suggest that PrP functions are more extensive than simple protective responses against stress insults.