Transmissibility of Creutzfeldt-Jakob disease and related disorders

The spongiform encephalopathies occur in both animals and humans, with kuru, Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, and Fatal Familial Insomnia constituting the currently recognised spectrum of such disorders in man. All have proven to be transmissible, including familial cases. Important determinants of transmissibility include the route of inoculation (intracerebral is most effective) and the titre of the inoculated material (brain and spinal cord have greatest infectivity). However, in familial cases, the pathogenic mutations in the PrP gene additionally influence the efficacy of transmission. Recent progress in the molecular biological basis of these diseases suggests that most of the infectivity resides in an abnormal, relatively protease resistant, isoform of the constitutively expressed PrP. The abnormal isoform is postulated to serve as a template for auto-catalytic polymerisation and the consequent deposition of amyloid. Extensions of this hypothesis attempt to reconcile the paradox of how these disorders can be both infectious and also inherited in an autosomal dominant fashion.