Pathologic prion protein is specifically recognized in situ by a novel PrP conformational antibody

Abstract

Prion diseases are characterized by the accumulation in the brain of abnormal conformers (PrPSc) of the cellular prion protein (PrPC).PrPSc immunohistochemistry, currently based on antibodies non-distinguishing between PrPC and PrPSc, requires pre-treatments of histological sections to eliminate PrPC and to denature PrPSc. We employed the PrPSc-specific antibody 89–112 PrP motif-grafted IgG on mildly fixed, untreated brain sections from several cases of human prion diseases. The results confirmed specific binding of IgG 89–112 to a structural determinant found exclusively on native disease-associated PrP conformations and lost following tissue denaturation or cross-linking fixation. Importantly, IgG 89–112 demonstrated no reactivity with normal brain tissue or with amyloid deposits in Alzheimer disease brain sections. Thus, immunohistochemical detection of native PrPSc deposits was obtained by means of a PrPSc-specific antibody. Such unique reagent may have many applications in the study of prion biology and in the diagnosis and prevention of prion diseases.