Prion diseases

Transmissible spongiform encephalopathies or prion diseases are chronic neurological disorders characterized by long incubation periods; progressive noninfl ammatory disease of brain and spinal cord; transmissibility within species and, to a limited extent, across species barriers; a failure of any immune response; and a uniformly fatal course. The pathology is characterized by neuronal loss, gliosis, and vacuoles in cytoplasm of neural cells giving the spongiform appearance on microscopic exam. Infectivity copurifi es with an isoform of a normal surface glycoprotein expressed primarily in the central nervous system. The function of the normal prion protein is unknown; but the misfolded protein—the prion—induces posttranslational conversion of normal prion protein with a helical structure into the infectious isoform rich in β-pleated sheets. This abnormal protease-resistant protein accumulates in brain leading to disease. To date no nucleic acid has been detected in the transmissible particle. Prion diseases are recognized in animals (scrapie, bovine spongiform encephalopathy, and chronic wasting disease of deer and elk) and humans (kuru, Creutzfeldt-Jakob disease [CJD], and the variant of CJD related to bovine spongiform encephalopathy). The human forms of disease can be divided into three groups: (1) sporadic CJD represents 85% to 90% of cases, (2) familial CJD due to mutations in the gene coding for prion protein making up 10% of cases, and (3) transmitted CJD due to iatrogenic transmission, cannibalism in the case of kuru, and, recently, transmission of bovine spongiform encephalopathy to humans.