title: Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification.
abstract: Six subtypes of sporadic Creutzfeldt-Jakob disease with distinctive clinico-pathological features have been identified largely based on two types of the abnormal prion protein, PrP(Sc), and the methionine (M)/valine (V) polymorphic codon 129 of the prion protein. The existence of affected subjects showing mixed phenotypic features and concurrent PrP(Sc) types has been reported but with inconsistencies among studies in both results and their interpretation. The issue currently complicates diagnosis and classification of cases and also has implications for disease pathogenesis. To explore the issue in depth, we carried out a systematic regional study in a large series of 225 cases. PrP(Sc) types 1 and 2 concurrence was detected in 35% of cases and was higher in MM than in MV or VV subjects. The deposition of either type 1 or 2, when concurrent, was not random and always characterized by the coexistence of phenotypic features previously described in the pure subtypes. PrP(Sc) type 1 accumulation and related pathology predominated in MM and MV cases, while the type 2 phenotype prevailed in VVs. Neuropathological examination best identified the mixed types 1 and 2 features in MMs and most MVs, and also uniquely revealed the co-occurrence of pathological variants sharing PrP(Sc) type 2. In contrast, molecular typing best detected the concurrent PrP(Sc) types in VV subjects and MV cases with kuru plaques. The present data provide an updated disease classification and are of importance for future epidemiologic and transmission studies aimed to identify etiology and extent of strain variation in sporadic Creutzfeldt-Jakob disease.
authors.affiliation: Dipartimento di Scienze Neurologiche, Università di Bologna, Bologna, Italy. piero.parchi@unibo.it
authors.forename: Piero
authors.initials: P
authors.lastname: Parchi
authors.forename: Rosaria
authors.initials: R
authors.lastname: Strammiello
authors.forename: Silvio
authors.initials: S
authors.lastname: Notari
authors.forename: Armin
authors.initials: A
authors.lastname: Giese
authors.forename: Jan P M
authors.initials: JP
authors.lastname: Langeveld
authors.forename: Anna
authors.initials: A
authors.lastname: Ladogana
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
authors.forename: Federico
authors.initials: F
authors.lastname: Roncaroli
authors.forename: Patrich
authors.initials: P
authors.lastname: Cras
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pocchiari
authors.forename: Hans
authors.initials: H
authors.lastname: Kretzschmar
authors.forename: Sabina
authors.initials: S
authors.lastname: Capellari
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000145:classification* / Q000453:epidemiology* / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009460:Neurologic Examination / Q000379:methods; D010641:Phenotype; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D018620:PrPSc Proteins / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D014633:Valine / Q000235:genetics
chemical_list: D018620:PrPSc Proteins; D008715:Methionine; D014633:Valine