NR AOPG
AU Satoh,K.; Muramoto,T.; Tanaka,T.; Kitamoto,N.; Ironside,J.W.; Nagashima,K.; Yamada,M.; Sato,T.; Mohri,S.; Kitamoto,T.
TI Association of an 11-12 kDa protease-resistant prion protein fragment with subtypes of dura graft-associated Creutzfeldt-Jakob disease and other prion diseases
QU Journal of General Virology 2003 Oct; 84(10): 2885-93
PT journal article
AB 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.
MH Adult; Aged; Brain/metabolism/pathology; Cadaver; Creutzfeldt-Jakob Syndrome/*classification/metabolism/pathology; Dura Mater/*transplantation; Female; Human; Male; Middle Age; PrPsc Proteins/classification/*metabolism; Prion Diseases/classification/pathology; Support, Non-U.S. Gov't
AD Department of Neurological Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Sendai 980-8575, Japan.
SP englisch
PO England