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

Piero Parchi, Rosaria Strammiello, Silvio Notari, Armin Giese, Jan P.M. Langeveld, Anna Ladogana, Inga Zerr, Federico Roncaroli, Patrich Cras, Bernardino Ghetti, Maurizio Pocchiari, Hans Kretzschmar, Sabina Capellari

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146 Scopus citations

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 PrPSc 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.

Original languageEnglish (US)
Pages (from-to)659-671
Number of pages13
JournalActa Neuropathologica
Volume118
Issue number5
DOIs
StatePublished - Nov 1 2009

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Keywords

  • Brain mapping
  • Classification
  • Molecular typing
  • Neurodegeneration
  • Prion protein

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Cellular and Molecular Neuroscience

Cite this

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. (2009). Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: An updated classification. Acta Neuropathologica, 118(5), 659-671. https://doi.org/10.1007/s00401-009-0585-1