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

Pedro Piccardo, Charles Seiler, Stephen Dlouhy, Katherine Young, Martin Farlow, Frances Prelli, Blas Frangione, Orso Bugiani, Fabrizio Tagliavini, Bernardino Ghetti

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Gerstmann-Straussler-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)1157-1163
Number of pages7
JournalJournal of Neuropathology and Experimental Neurology
Volume55
Issue number11
StatePublished - Nov 1996

Fingerprint

Gerstmann-Straussler-Scheinker Disease
Endopeptidase K
Protein Isoforms
Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
Amyloidogenic Proteins
Congo Red
Mutation
Prion Diseases
Caudate Nucleus
Amyloid Plaques
Brain
Amyloidosis
Prion Proteins
Amyloid
Codon
Cerebellum
Fluorescence
Immunohistochemistry
Pathology

Keywords

  • Amyloid
  • Antibodies
  • Gerstmann-Straussler-Scheinker (GSS) disease
  • Immunoblot
  • Prion protein (PrP)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Proteinase-K-resistant prion protein isoforms in Gerstmann-Straussler- Scheinker disease (Indiana kindred). / Piccardo, Pedro; Seiler, Charles; Dlouhy, Stephen; Young, Katherine; Farlow, Martin; Prelli, Frances; Frangione, Blas; Bugiani, Orso; Tagliavini, Fabrizio; Ghetti, Bernardino.

In: Journal of Neuropathology and Experimental Neurology, Vol. 55, No. 11, 11.1996, p. 1157-1163.

Research output: Contribution to journalArticle

Piccardo, P, Seiler, C, Dlouhy, S, Young, K, Farlow, M, Prelli, F, Frangione, B, Bugiani, O, Tagliavini, F & Ghetti, B 1996, 'Proteinase-K-resistant prion protein isoforms in Gerstmann-Straussler- Scheinker disease (Indiana kindred)', Journal of Neuropathology and Experimental Neurology, vol. 55, no. 11, pp. 1157-1163.
Piccardo, Pedro ; Seiler, Charles ; Dlouhy, Stephen ; Young, Katherine ; Farlow, Martin ; Prelli, Frances ; Frangione, Blas ; Bugiani, Orso ; Tagliavini, Fabrizio ; Ghetti, Bernardino. / Proteinase-K-resistant prion protein isoforms in Gerstmann-Straussler- Scheinker disease (Indiana kindred). In: Journal of Neuropathology and Experimental Neurology. 1996 ; Vol. 55, No. 11. pp. 1157-1163.
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