Determinants of Creutzfeldt-Jakob disease : a genetic epidemiologic study

Abstract

Creutzfeldt-Jakob disease (CJD) is the most common form of the human transmissible spongiform encephalopathies.1 The disease is characterised by rapid neurodegeneration leading to death within weeks to months. CJD is a rare disorder with an intriguing etiology, involving genetic and iatrogenic transmission. Ten to fifteen percent of patients with CJD are determined by mutations in the prion protein gene.2 The clinical expression of these familial forms is highly variable and may range from a ‘typical’ CJD phenotype with rapid deterioration to a slowly progressive dementia mimicking Alzheimer’s disease. Apart from the causative mutations, a common polymorphism within the prion protein gene determines susceptibility to CJD.3 Subjects who are homozygous for either allele of this polymorphism are at increased risk of CJD. There is growing evidence that this polymorphism further may influence clinical expression of CJD. Finally, the effect of the prion protein may extend to other forms of neurodegenerative disorders. Besides a role in rare diseases such as Gerstmann-Sträussler-Scheinker disease and fatal familial insomnia, the gene may also have an effect on cognitive decline and dementia in the general populatio