1. Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of <tex>PrP^{Sc}$</tex>: an updated classification
- Author
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Hans A. Kretzschmar, Maurizio Pocchiari, Rosaria Strammiello, Federico Roncaroli, Patrich Cras, Armin Giese, Piero Parchi, Silvio Notari, Bernardino Ghetti, Jan P. M. Langeveld, Anna Ladogana, Inga Zerr, Sabina Capellari, Parchi P, Strammiello R, Notari S, Giese A, Langeveld JP, Ladogana A, Zerr I, Roncaroli F, Cras P, Ghetti B, Pocchiari M, Kretzschmar H, and Capellari S.
- Subjects
Male ,Pathology ,molecular-basis ,PrPSc Proteins ,animal diseases ,DNA Mutational Analysis ,Plaque, Amyloid ,Disease ,Molecular typing ,Creutzfeldt-Jakob Syndrome ,0302 clinical medicine ,Methionine ,abnormal prion protein ,Genetics ,Aged, 80 and over ,Neurologic Examination ,0303 health sciences ,fatal familial insomnia ,Incidence ,Bacteriologie ,Brain ,Valine ,Bacteriology, Host Pathogen Interaction & Diagnostics ,Middle Aged ,Classification ,Phenotype ,Prion protein ,Brain mapping ,Neurodegeneration ,3. Good health ,Kuru ,conformations ,Female ,medicine.medical_specialty ,Clinical Neurology ,western-blot ,Biology ,Pathology and Forensic Medicine ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,cjd ,scrapie strains ,medicine ,Humans ,Pathological ,030304 developmental biology ,Aged ,Retrospective Studies ,brain-tissue ,Fatal familial insomnia ,Host Pathogen Interaction & Diagnostics ,Original Paper ,Bacteriology ,medicine.disease ,Host Pathogen Interactie & Diagnostiek ,strain variation ,nervous system diseases ,Bacteriologie, Host Pathogen Interactie & Diagnostiek ,Etiology ,Medicine & Public Health ,Neurosciences ,identification ,Neurology (clinical) ,Human medicine ,030217 neurology & neurosurgery - 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, PrPSc, and the methionine (M)/valine (V) polymorphic codon 129 of the prion protein. The existence of affected subjects showing mixed phenotypic features and concurrent PrPp. 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. PrPSc 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. PrPSc 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 PrPSc type 2. In contrast, molecular typing best detected the concurrent PrPSc 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. peerReviewed
- Published
- 2009