Novel prion protein conformation and glycotype in Creutzfeldt-Jakob disease.

OBJECTIVE To describe a novel molecular and pathological phenotype of Creutzfeldt-Jakob disease. Patient A 69-year-old woman with behavioral and personality changes followed by rapidly evolving dementia. RESULTS Postmortem examination of the brain showed intracellular prion protein deposition and axonal swellings filled with amyloid fibrils. Biochemical analysis of the pathological prion protein disclosed a previously unrecognized PrP(Sc) tertiary structure lacking diglycosylated species. Genetic analysis revealed a wild-type prion protein gene. The prion agent responsible for this atypical phenotype was successfully passaged to bank voles. CONCLUSION To our knowledge, our results define a new human prion disorder characterized by intracellular accumulation of a novel type of pathological prion protein.