Neuropathology of variant Creutzfeldt-Jakob disease

The neuropathological features human prion diseases comprise spongiform change, neuronal loss, astrocytic and microglial proliferation and the accumulation of the abnormal isoform of prion protein (PrPRES) in the central nervous system. Variant Creutzfeldt-Jakob disease (CJD) is a novel human prion disease which appears to result from infection by the bovine spongiform encephalopathy (BSE) agent. The neuropathology of variant CJD shows morphological and immunocytochemical characteristics distinct from all other types of human prion disease, and is characterised by abundant florid and cluster plaques in the cerebrum and cerebellum, and widespread accumulation of PrPRES on immunocytochemistry. Spongiform change is most marked in the caudate nucleus and putamen, and the thalamus exhibits severe neuronal loss and gliosis, which is most marked in the posterior nuclei and correlates with the areas of high signal seen in the posterior thalamus on MRI examination of the brain. Western blot analysis of PrPRES on frozen brain tissue in variant CJD tissue shows a uniform isotype, with a glycoform ratio distinct from sporadic CJD. PrPRES accumulation is widespread in lymphoid tissues in vCJD. All cases of variant CJD are methionine homozygotes at codon 129 of the PrP gene. Histological and biochemical techniques will be required to identify cases of 'human BSE' in individuals who are MV or VV at codon 129 of the PrP gene. Continued surveillance is required to investigate this possibility in the UK and other countries where BSE has been reported.