Four separate types of Creutzfeldt-Jakob disease?
Researchers from the UK and France have identified four separate biochemical subgroups in a selection of cases of Creutzfeldt-Jakob disease. The study suggests that these subgroups could represent distinct prion strains in what is the most common human prion disease. Prion diseases are transmissible neurodegenerative disorders characterized by accumulation of an abnormal isoform (PrPSc) of a host-encoded protein (PrPC) in affected tissues. According to the prion hypothesis, PrPSc alone constitutes the infectious agent. Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest human prion disease. Although considered as a spontaneous disorder, the clinicopathological phenotype of sCJD is variable and substantially influenced by the methionine/valine polymorphism at codon 129 of the prion protein gene (PRNP). Based on these clinicopathological and genetic criteria, a subclassification of sCJD has been proposed. Two new biochemical assays identified four distinct biochemical PrPSc subgroups in a cohort of 41 sCJD cases. These subgroups correlate with the current sCJD subclassification and could therefore represent distinct prion strains. Iatrogenic CJD (iCJD) occurs following presumed accidental human-to-human sCJD transmission. Our biochemical investigations on 12 iCJD cases from different countries found the same four subgroups as in sCJD. However, in contrast to the sCJD cases, no particular correlation between the PRNP codon 129 polymorphism and biochemical PrPSc phenotype could be established in iCJD cases. This study provides an alternative biochemical definition of PrPSc diversity in human prion diseases and new insights into the perception of agent variability.
Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres) identified on Western blotting (type 1 or type 2). These biochemically distinct PrPres types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrPres in the brain, the basis of this classification system and its relationship to agent strain are under discussion. The identification of four different PrPSc biochemical subgroups in sCJD and iatrogenic CJD (iCJD), irrespective of the PRNP polymorphism at codon 129 and the PrPres isoform, provides an alternative biochemical definition of PrPSc diversity and new insight in the perception of Human TSE agents variability.
Beyond PrPres Type 1/Type 2 Dichotomy in Creutzfeldt-Jakob Disease. PLoS Pathog 4(3): e1000029
Related:
- Drugs for treatment of prion infections
- Fears over new wave of vCJD deaths
- A General Model of Prion Strains and Their Pathogenicity
- Prions, Proteasomes, and Mad Cows
Tags: Biology, Health, Medicine, Microbiology, Prions, Science
On the PRNP front, it’s also worth flagging up this new TSE related Paper in PLoS ONE by Clawson et al.