Pathology of Variant Creutzfeldt-Jakob Disease

Summary

Variant Creutzfeldt-Jakob disease (CJD) is a novel form of human prion disease that appears to result from oral infection by the bovine spongiform encephalopathy (BSE) agent. Variant CJD is also unique in human prion diseases in that infectivity and accumulation of the disease-associated isoform of prion protein are readily detectable outside the central nervous system, perhaps reflecting the peripheral pathogenesis of this disorder following an oral infection with BSE. The neuropathological features of variant CJD are unique in terms of the histological features and the biochemical features of the abnormal isoform of prion protein in the brain and in lymphoid tissues. This peripheral accumulation of infectivity has also resulted in the apparent iatrogenic transmission of variant CJD on 2 occasions, following a transfusion with non-leucodepleted red blood cells from donors who subsequently died from variant CJD. All clinical cases of variant CJD have so far occurred in individuals who are methionine homozygotes at codon 129 in the prion protein gene. However, one of the iatrogenic infections occurred in an individual who is heterozygous at this locus, indicating the future clinical cases might also occur in this group. Continuing surveillance of all forms of CJD is required to address this possibility, not just in the UK but in other countries either with or at risk of cases of BSE in the cattle population.