Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification

• Published in: Acta neuropathologica Vol. 118; no. 5; pp. 659 - 671
• Main Authors: Parchi, P, Strammiello, R, Notari, S, Giese, A, Langeveld, J.P.M, Ladogana, A, Zerr, I, Roncaroli, F, Cras, P, Ghetti, B, Pocchiari, M, Kretzschmar, H, Capellari, S
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.11.2009; Springer Nature B.V
• Subjects: abnormal prion protein; Aged; Aged, 80 and over; Brain - metabolism; Brain - pathology; brain-tissue; cjd; conformations; Creutzfeldt-Jakob Syndrome - classification; Creutzfeldt-Jakob Syndrome - epidemiology; Creutzfeldt-Jakob Syndrome - pathology; Creutzfeldt-Jakob Syndrome - physiopathology; Disease; DNA Mutational Analysis - methods; fatal familial insomnia; Female; Genotype & phenotype; Humans; identification; Incidence; Male; Medicine; Medicine & Public Health; Methionine - genetics; Middle Aged; molecular-basis; Neurologic Examination - methods; Neurosciences; Original Paper; Pathology; Phenotype; Plaque, Amyloid - metabolism; Plaque, Amyloid - pathology; Proteins; PrPSc Proteins - classification; PrPSc Proteins - genetics; PrPSc Proteins - metabolism; Retrospective Studies; scrapie strains; strain variation; Valine - genetics; western-blot; Germany; Molecular typing; Prion protein; Neurodegeneration; Brain mapping; Classification
• ISSN: 0001-6322; 1432-0533; 1432-0533
• DOI: 10.1007/s00401-009-0585-1

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.