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.
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