Association of an 11 - 12 kDa protease-resistant prion protein fragment with subtypes of dura graft-associated Creutzfeldt-Jakob disease and other prion diseases

Katsuya Satoh, Tamaki Muramoto, Tomoyuki Tanaka, Noritoshi Kitamoto, James W. Ironside, Kazuo Nagashima, Masahito Yamada, Takeshi Sato, Shirou Mohri, Tetsuyuki Kitamoto

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

Creutzfeldt-Jakob disease can develop in subjects given a cadaveric dura mater graft (dCJD). This disease has a phenotypic heterogeneity despite the lack of genetic variation. Numerous plaque-type prion protein (PrP) deposits are found in the brain of some but not all subjects; hence, there may be two subtypes of this clinical entity. To validate dCJD subtypes further, we carried out a larger-scale clinicopathological analysis and typing of protease-resistant PrP (PrPSc) in dCJD cases. Cases with plaque-type PrP deposits (p-dCJD) were shown to be distinct from those without PrP plaques (np-dCJD), from several clinicopathological aspects. Analysis of PrPSc revealed that, while the major PrPSc species from both subtypes was of 21 kDa after deglycosylation (type 1 PrPSc), a C-terminal PrP fragment of 11-12 kDa (fPrP11-12) was associated with np-dCJD but not with p-dCJD. The disease type-specific association of fPrP11-12 was also observed in subjects with other prion diseases. An fPrP11-12-like C-terminal PrP fragment was detected in brain lysates from patients associated with fPrP11-12, but not from patients or normal subjects unassociated with fPrP11-12. Results indicated that fPrP was produced by CJD-associated processes in vivo. The present data provide several lines of evidence that support the need for subtyping of dCJD and contribute to the understanding of the processing of disease-specific PrP species. The unique relationship of fPrP11-12 with CJD phenotype supports the view that the phenotypic heterogeneity of CJD is related to the formation of different types of disease-specific PrP and fragments thereof.

Original languageEnglish
Pages (from-to)2885-2893
Number of pages9
JournalJournal of General Virology
Volume84
Issue number10
DOIs
Publication statusPublished - 2003 Oct 1

ASJC Scopus subject areas

  • Virology

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