Prion protein and developments in its detection.

Abstract

The theoretical risk of transmission of variant Creutzfeldt-Jakob disease (vCJD) via blood transfusions has led to replacement of UK-derived plasma for fractionation by plasma sourced outwith the UK and the introduction of leucodepletion of donated blood and its components. Prion protein in an abnormal conformation (PrPsc) has been identified as inextricably linked with the infectivity of transmissible spongiform encephalopathies such as vCJD and in this review some of its properties relevant to its detection are considered. In particular its insolubility in nonionic detergents and its partial resistance to proteinase K digestion have provided methods for separating it from the normal abundant isoform PrPc prior to subsequent detection, usually by means of antibody probes. As yet no antibodies which discriminate between the abnormal and normal isoforms have been identified with the sole exception of one which is not suitable for generally used immunodetection systems. Most detection systems, such as immunohistochemistry or Western blotting, have been optimized for brain or lympho-reticular tissues. Much less information is available for assays applied to blood or plasma, although some recent publications provide indications of their feasibility. However, a number of obstacles remain to be overcome. These include the issues of assay validation, detection of extremely low levels of PrPsc in the presence of large excesses of PrPc, lack of available standardized reagents, assay specificity and practicality for large-scale screening use. Progress towards these goals is reviewed.