NR AJLD
AU Piccardo,P.; Seiler,C.; Dlouhy,S.R.; Young,K.; Farlow,M.R.; Prelli,F.; Frangione,B.; Bugiani,O.; Tagliavini,F.; Ghetti,B.
TI Proteinase-K-resistant prion protein isoforms in Gerstmann-Sträussler-Scheinker disease (Indiana kindred)
QU Journal of Neuropathology and Experimental Neurology 1996 Nov; 55(11): 1157-63
PT journal article
AB Gerstmann-Sträussler-Scheinker (GSS) disease is a cerebral prion protein (PrP) amyloidosis associated with mutations in the PrP gene (PRNP). A GSS disease variant with mutation at codon 198 (F198S) has been studied in a large Indiana kindred. Biochemical investigations showed that the amyloid protein consists of 11 and 7 kDa fragments of PrP. Immunohistochemical studies showed that in addition to amyloid, these patients accumulate PrP deposits which are neither fluorescent nor birefringent when stained with thioflavin S and Congo red. In the present paper, we analyzed proteinase-K (PK)-resistant PrP in 7 patients with GSS F198S disease. Immunoblots of PK-treated brain extracts show prominent bands of ca. 27-29, 18-19, and 8 kDa. Immunohistochemistry and thioflavin-S-fluorescence show that the amyloid deposits are conspicuous in the cerebellum but sparse in the caudate nucleus. However, immunoblot analysis reveals PK-resistant PrP bands of similar intensity in both regions. Treatment with PK and PNGase F generates a pattern similar to that of PK alone. Our findings suggest that brain extracts from GSS F198S disease contain 3 prominent nonglycosylated PK-resistant PrP fragments forming a pattern not previously described in other prion diseases, which may in part explain the pathology of this GSS disease variant.
MH Adult; Aged; Amyloid/metabolism; Brain/metabolism/pathology; Creutzfeldt-Jakob Syndrome/metabolism/pathology; Drug Resistance; Endopeptidase K/*pharmacology; Gerstmann-Sträussler-Scheinker Disease/genetics/*metabolism/pathology; Human; Immunoblotting; Isomerism; Middle Age; Prions/*drug effects/*metabolism; Subcellular Fractions/metabolism; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Department of Pathology, Indiana University School of Medicine, Indianapolis 46202-5120, USA
SP englisch
PO USA