Phenotypic variability of Gerstmann-Straussler-Scheinker disease is associated with prion protein heterogeneity

Pedro Piccardo, Stephen R. Dlouhy, Patricia M.J. Lievens, Katherine Young, Thomas D. Bird, David Nochlin, Dennis W. Dickson, Harry V. Vinters, Thomas R. Zimmerman, Ian R.A. Mackenzie, Stephen J. Kish, Lee Cyn Ang, Charles De Carli, Maurizio Pocchiari, Paul Brown, Clarence J. Gibbs, D. Carlton Gajdusek, Orso Bugiani, James Ironside, Fabrizio TagliaviniBernardino Ghetti

Research output: Contribution to journalArticlepeer-review

172 Scopus citations


Gerstmann-Straussler-Scheinker disease (GSS), a cerebello-pyramidal syndrome associated with dementia and caused by mutations in the prion protein gene (PRNP), is phenotypically heterogeneous. The molecular mechanisms responsible for such heterogeneity are unknown. Since we hypothesize that prion protein (PrP) heterogeneity may be associated with clinico-pathologic heterogeneity, the aim of this study was to analyze PrP in several GSS variants. Among the pathologic phenotypes of GSS, we recognize those without and with marked spongiform degeneration. In the latter (i.e. a subset of GSS P102L patients) we observed 3 major proteinase-K resistant PrP (PrPres) isoforms of ca. 21-30 kDa, similar to those seen in Creutzfeldt- Jakob disease. In contrast, the 21-30 kDa isoforms were not prominent in GSS variants without spongiform changes, including GSS A117V, GSS D202N, GSS Q212P, GSS Q217R, and 2 cases of GSS P102L. This suggests that spongiform changes in GSS are related to the presence of high levels of these distinct 21-30 kDa isoforms. Variable amounts of smaller, distinct PrPres isoforms of ca. 7-15 kDa were seen in all GSS variants. This suggests that GSS is characterized by the presence PrP isoforms that can be partially cleaved to low molecular weight PrPres peptides.

Original languageEnglish (US)
Pages (from-to)979-988
Number of pages10
JournalJournal of Neuropathology and Experimental Neurology
Issue number10
StatePublished - Oct 1998


  • Gerstmann-Straussler-Scheinker disease (GSS)
  • Immunoblot
  • PrP gene (PRNP)
  • Prion protein (PrP)

ASJC Scopus subject areas

  • Medicine(all)


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