title: Neuropathological and biochemical criteria to identify acquired Creutzfeldt-Jakob disease among presumed sporadic cases.
abstract: As an experimental model of acquired Creutzfeldt-Jakob disease (CJD), we performed transmission studies of sporadic CJD using knock-in mice expressing human prion protein (PrP). In this model, the inoculation of the sporadic CJD strain V2 into animals homozygous for methionine at polymorphic codon 129 (129 M/M) of the PRNP gene produced quite distinctive neuropathological and biochemical features, that is, widespread kuru plaques and intermediate type abnormal PrP (PrP(Sc) ). Interestingly, this distinctive combination of molecular and pathological features has been, to date, observed in acquired CJD but not in sporadic CJD. Assuming that these distinctive phenotypic traits are specific for acquired CJD, we revisited the literature and found two cases showing widespread kuru plaques despite the 129 M/M genotype, in a neurosurgeon and in a patient with a medical history of neurosurgery without dura mater grafting. By Western blot analysis of brain homogenates, we revealed the intermediate type of PrP(Sc) in both cases. Furthermore, transmission properties of brain extracts from these two cases were indistinguishable from those of a subgroup of dura mater graft-associated iatrogenic CJD caused by infection with the sporadic CJD strain V2. These data strongly suggest that the two atypical CJD cases, previously thought to represent sporadic CJD, very likely acquired the disease through exposure to prion-contaminated brain tissues. Thus, we propose that the distinctive combination of 129 M/M genotype, kuru plaques, and intermediate type PrP(Sc) , represents a reliable criterion for the identification of acquired CJD cases among presumed sporadic cases.
authors.affiliation: Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan.|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.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: Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Shirou
authors.initials: S
authors.lastname: Mohri
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: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D003062:Codon; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D055879:Gene Knock-In Techniques; D005838:Genotype; D006801:Humans; D008715:Methionine / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D018621:PrPC Proteins / Q000235:genetics; D018620:PrPSc Proteins / Q000235:genetics; D000072002:Prion Proteins / Q000235:genetics*
chemical_list: D003062:Codon; C512656:PRNP protein, human; D018621:PrPC Proteins; D018620:PrPSc Proteins; D000072002:Prion Proteins; D008715:Methionine
keywords: Creutzfeldt-Jakob disease; PRNP; iatrogenic; prion diseases; prions