title: Distinctive properties of plaque-type dura mater graft-associated Creutzfeldt-Jakob disease in cell-protein misfolding cyclic amplification.
abstract: There are two distinct subtypes of dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) with methionine homozygosity at codon 129 of the PRNP gene. The majority of cases is represented by a non-plaque-type (np-dCJD) resembling sporadic CJD (sCJD)-MM1 or -MV1, while the minority by a plaque-type (p-dCJD). p-dCJD shows distinctive phenotypic features, namely numerous kuru plaques and an abnormal isoform of prion protein (PrP(Sc)) intermediate in size between types 1 and 2. Transmission studies have shown that the unusual phenotypic features of p-dCJD are linked to the V2 prion strain that is associated with sCJD subtypes VV2 or -MV2. In this study, we applied protein misfolding cyclic amplification (PMCA) using recombinant human prion protein as a substrate and demonstrated that p-dCJD prions show amplification features that are distinct from those of np-dCJD. Although no amplification of np-dCJD prions was observed with either 129 M or 129 V substrate, p-dCJD prions were drastically amplified with the 129 V substrates, despite the PRNP codon 129 incompatibility between seed and substrate. Moreover, by using a type 2 PrP(Sc)-specific antibody not recognizing PrP(Sc) in p-dCJD, we found that type 2 products are generated de novo from p-dCJD prions during PMCA with the 129 V substrates. These findings suggest that our cell-PMCA is a useful tool for easily and rapidly identifying acquired CJD associated with the transmission of the V2 CJD strain to codon 129 methionine homozygotes, based on the preference for the 129 V substrate and the type of the amplified products.
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Takeuchi
authors.affiliation: Laboratory of Comparative Pathology, Hokkaido University, Graduate School of Veterinary Medicine, Sapporo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: IRCCS, Istituto delle Scienze Neurologiche, Bologna, Italy.|Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Piero
authors.identifier: 0000-0002-9444-9524
authors.initials: P
authors.lastname: Parchi
authors.affiliation: Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Research and Development Division, Japan Blood Products Organization, Tokyo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Morita
authors.affiliation: Research and Development Division, Japan Blood Products Organization, Tokyo, Japan.
authors.forename: Shusei
authors.initials: S
authors.lastname: Uno
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Kitamoto
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology; D003062:Codon; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics* / Q000378:metabolism* / Q000635:transmission; D004388:Dura Mater / Q000637:transplantation*; D006720:Homozygote; D006801:Humans; D008715:Methionine / Q000737:chemistry / Q000235:genetics; D018620:PrPSc Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000072002:Prion Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017510:Protein Folding; D014633:Valine / Q000737:chemistry / Q000235:genetics
chemical_list: D003062:Codon; C512656:PRNP protein, human; D018620:PrPSc Proteins; D000072002:Prion Proteins; D008715:Methionine; D014633:Valine