Prospects for the development of pre-mortem laboratory diagnostic tests for Creutzfeldt-Jakob disease

At present the diagnosis of Creutzfeldt-Jakob disease (CJD) and related transmissible spongiform encephalopathies in humans is based on clinical criteria and (at post-mortem) the histopathological and immunological examination of brain tissue. The misfolded prion protein, PrPSc, is the single most significant marker, but its recognition by standard serological methods is complicated by its antigenic similarity to the normal prion protein, PrPC. Although there are commercial diagnostic assays available for bovine spongiform encephalopathy using brain specimens taken at slaughter, there are no suitable pre-mortem assays for cattle and none either for pre-mortem human disease. Especially in view of the recent report of variant CJD transmission by blood transfusion, it is important that tests for pre-symptomatic infections are developed. This will safeguard the blood supply and, for example, prevent the transmission of CJD in neurosurgery. This paper reviews the current and prospective approaches to the pre-mortem diagnosis of CJD, in particular its variant form.