Association of an 11-12 kDa protease-resistant prion protein fragment with subtypes of dura graft-associated Creutzfeldt-Jakob disease and other prion diseases.
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 (PrP(Sc)) 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 PrP(Sc) revealed that, while the major PrP(Sc) species from both subtypes was of 21 kDa after deglycosylation (type 1 PrP(Sc)), 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.
D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002102:Cadaver; D007562:Creutzfeldt-Jakob Syndrome / Q000145:classification* / Q000378:metabolism / Q000473:pathology; D004388:Dura Mater / Q000637:transplantation*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018620:PrPSc Proteins / Q000145:classification / Q000378:metabolism*; D017096:Prion Diseases / Q000145:classification / Q000473:pathology
D018620:PrPSc Proteins