Prion protein preamyloid and amyloid deposits in Gerstmann-Sträussler-Scheinker disease, Indiana kindred

Giorgio Giaccone, Laura Verga, Orso Bugiani, Blas Frangione, Dan Serban, Stanley B. Prusiner, Martin Farlow, Bernardino Ghetti, Fabrizio Tagliavini

Research output: Contribution to journalArticle

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Abstract

Gerstmann-Sträussler-Scheinker disease (GSS) is a familial neurological disorder pathologically characterized by amyloid deposition in the cerebrum and cerebellum. In GSS, the amyloid is immunoreactive to antisera raised against the prion protein (PrP) 27-30, a proteinase K-resistant peptide of 27-30 kDa that is derived by limited proteolysis from an abnormal isoform of a neuronal sialoglycoprotein of 33-35 kDa designated PrPSc. Polyclonal antibodies raised against synthetic peptides homologous to residues 15-40 (P2), 90-102 (P1), and 220-232 (P3) of the amino acid sequence deduced from hamster PrP cDNA were used to investigate immunohistochemically the distribution of PrP and PrP fragments in the brains of two patients from the Indiana kindred of GSS. Two types of anti-PrP-immunoreactive deposits were found: (i) amyloid deposits, which were exclusively labeled by anti-P1 antiserum to residues 90-102 of PrP, and (ii) preamyloid deposits, which were labeled by all anti-PrP antisera but did not exhibit the tinctorial and optical properties of amyloid. The latter appeared as diffuse immunostaining of the neuropil that targeted to areas in which amyloid deposits were most abundant. They were partially resistant to proteinase K digestion and consisted ultrastructurally of amorphous, flaky, electron-dense material. These findings substantiate our previous observation that the major amyloid component in the GSS Indiana kindred is an internal fragment of PrP and indicate that full-length abnormal isoforms of PrP and/or large PrP fragments accumulate in brain regions most affected by amyloid deposition. These findings support the view that in the GSS Indiana kindred a stepwise degradation of PrP occurs in situ in the process of amyloid fibril formation.

Original languageEnglish
Pages (from-to)9349-9353
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number19
StatePublished - Oct 1 1992

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Amyloid Plaques
Amyloid
Immune Sera
Endopeptidase K
Protein Isoforms
Prion Proteins
Sialoglycoproteins
Peptides
Neuropil
Brain
Cerebrum
Nervous System Diseases
Cricetinae
Cerebellum
Proteolysis
Digestion
Amino Acid Sequence
Complementary DNA
Electrons
Staining and Labeling

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Giaccone, G., Verga, L., Bugiani, O., Frangione, B., Serban, D., Prusiner, S. B., ... Tagliavini, F. (1992). Prion protein preamyloid and amyloid deposits in Gerstmann-Sträussler-Scheinker disease, Indiana kindred. Proceedings of the National Academy of Sciences of the United States of America, 89(19), 9349-9353.

Prion protein preamyloid and amyloid deposits in Gerstmann-Sträussler-Scheinker disease, Indiana kindred. / Giaccone, Giorgio; Verga, Laura; Bugiani, Orso; Frangione, Blas; Serban, Dan; Prusiner, Stanley B.; Farlow, Martin; Ghetti, Bernardino; Tagliavini, Fabrizio.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 89, No. 19, 01.10.1992, p. 9349-9353.

Research output: Contribution to journalArticle

Giaccone, Giorgio ; Verga, Laura ; Bugiani, Orso ; Frangione, Blas ; Serban, Dan ; Prusiner, Stanley B. ; Farlow, Martin ; Ghetti, Bernardino ; Tagliavini, Fabrizio. / Prion protein preamyloid and amyloid deposits in Gerstmann-Sträussler-Scheinker disease, Indiana kindred. In: Proceedings of the National Academy of Sciences of the United States of America. 1992 ; Vol. 89, No. 19. pp. 9349-9353.
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