ULTRASTRUCTURAL IMMUNO-LOCALIZATION OF SYNTHETIC PRION PROTEIN PEPTIDE ANTIBODIES IN 87V MURINE SCRAPIE

Disease specific forms of a host encoded cell surface sialoglycoprotei n called prion protein (PrP) accumulate during the incubation period o f the transmissible spongiform encephalopathies. A 33-35 kDa disease s pecific form of PrP is partially resistant to protease digestion where as the normal form of PrP can be completely digested. Proteinase K dig estion of the murine disease specific form of PrP produces diverse for ms of low molecular weight PrP, some of which are N-terminally truncat ed at amino acid residue 49 or 57 within the octapeptide repeat segmen t. Amyloid plaques are a pathological feature of many of the transmiss ible spongiform encephalopathies and are composed of PrP. Using synthe tic peptide antibodies to the N-terminus of PrP (which is not present in truncated disease specific PrP) and antibodies to the protease resi stant fraction of PrP we have immunostained plaques and pre-amyloid de posits in the brains of mice, experimentally infected with the 87V str ain of scrapie, for examination by light and electron microscopy. Clas sical fibrillar amyloid deposits in plaques as well as pre-amyloid dep osits were both immunostained by antibodies to the N-terminus of PrP a nd to the protease resistant core of the PrP molecule. This suggests t hat both N-terminal and core amino acid residues are present in diseas e specific PrP released from scrapie infected cells in vivo. The resul ts also suggest that N-terminal truncation of PrP may not be essential for formation of amyloid fibrils. (C) 1996 Academic Press Limited.