Proteinase-K-resistant prion protein isoforms in Gerstmann-Sträussler-Scheinker disease (Indiana kindred)

P Piccardo, C Seiler, S R Dlouhy, K Young, M R Farlow, F Prelli, B Frangione, O Bugiani, F Tagliavini, B Ghetti

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1157-63
Number of pages7
JournalJournal of Neuropathology and Experimental Neurology
Volume55
Issue number11
Publication statusPublished - Nov 1996

Keywords

  • Adult
  • Aged
  • Amyloid
  • Brain
  • Creutzfeldt-Jakob Syndrome
  • Drug Resistance
  • Endopeptidase K
  • Gerstmann-Straussler-Scheinker Disease
  • Humans
  • Immunoblotting
  • Isomerism
  • Middle Aged
  • Prions
  • Subcellular Fractions

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