GERSTMANN-STRAUSSLER-SCHEINKER DISEASE (PRNP P102L) - AMYLOID DEPOSITS ARE BEST RECOGNIZED BY ANTIBODIES DIRECTED TO EPITOPES IN PRP REGION90-165

Gerstmann-Straussler-Scheinker (GSS) disease is a familial neurologica l disorder pathologically characterized by accumulation of prion prote in (PrP) in the form of fibrillary and non-fibrillary deposits within the cerebrum and cerebellum. We have studied two patients in whom the disease is caused by a leucine for proline amino acid substitution at residue 102 of PrP. In both patients, me neuropathologic findings are similar, consisting of spongiform changes, amyloid deposits, and glios is. To investigate the antigenic profile of PrP deposits, we used anti bodies raised against several peptides that correspond to segments of the N-terminus, repeat region, midregion, and C-terminus of PrP. By im munohistochemistry, PrP amyloid cores are best labeled by antibodies d irected to epitopes spanning PrP residues 90-165. In GSS disease cause d by a substitution of thymine to cytosine at PRNP codon 198 (Indiana kindred), the major amyloidogenic peptide spans residues 58-150; there fore, in these two genetic forms of GSS disease, amyloid may be compos ed of different peptides.