Neuropathology and Molecular Biology of Variant Creutzfeldt-Jakob Disease

  • J. W. Ironside
  • M. W. Head
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 284)


The neuropathological features of human prion diseases are spongiform change, neuronal loss, astrocytic proliferation and the accumulation of PrPSc, the abnormal isoform of prion protein (PrP). The pattern of brain involvement is remarkably variable and is substantially influenced by the host PrP genotype and PrPSc isotype. Variant Creutzfeldt-Jakob disease (vCJD) is a novel human prion disease which results from exposure to the bovine spongiform encephalopathy (BSE) agent. The neuropathology of vCJD shows consistent characteristics, with abundant florid and cluster plaques in the cerebrum and cerebellum, and widespread accumulation of PrPres on immunocytochemistry. These features are distinct from all other types of human prion disease. Spongiform change is most marked in the basal ganglia, while the thalamus exhibits severe neuronal loss and gliosis in the posterior nuclei. These areas of thalamic pathology correlate with the areas of high signal seen in the thalamus on magnetic resonance imaging (MRI) examination of the brain. Western blot analysis of PrPSc in the brain in vCJD tissue shows a uniform isotype, with a glycoform ratio characterized by predominance of the diglycosylated band, distinct from sporadic CJD. PrPSc accumulation in vCJD is readily detectable outside the brain, in contrast with other forms of human prion disease, particularly in the lymphoid system and in parts of the peripheral nervous system. This has raised concern about the possible iatrogenic transmission of vCJD by contaminated surgical instruments, or blood. All cases of vCJD are methionine homozygotes at codon 129 of the prion protein gene (PRNP). Continued surveillance is required to investigate cases of vCJD in the UK and other countries where BSE has been reported, particularly as cases of ‘human BSE’ in individuals who are MV or VV at codon 129 of the PrP gene have not yet been identified. Histological, genetic and biochemical techniques are essential tools for the adequate diagnosis and investigation of human prion diseases.


Prion Protein Prion Disease Bovine Spongiform Encephalopathy PRNP Gene Fatal Familial Insomnia 
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Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • J. W. Ironside
    • 1
  • M. W. Head
    • 1
  1. 1.National Creutzfeldt-Jakob Disease Surveillance Unit, Department of Pathology, Western General HospitalUniversity of EdinburghEdinburghUK

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