Human Prion Disease

Human spongiform encephalopathies are rare, fatal diseases characterized by rapid degeneration of the central nervous system. According to current theory, the responsible pathogen is an unconventional agent or "prion", thought to derive from a normal constituent of the cell membrane, which undergoes post-translational modification. The pathophysiology remains controversial and a subject of intense investigation. The classic triad of morphologic changes consists of spongiform change, gliosis and neuronal loss. Although infectious, spongiform encephalopathies are not associated with inflammation, viral inclusions, viral particles, or antiviral antibodies.

Although the overall incidence is only 1 per million, Creutzfeldt-Jacob disease (CJD), is the most common of the human diseases, accounting for approximately 95% of total cases. Modes of transmission include sporadic, inherited, iatrogenic, and variant CJD (vCJD). Other less common human prion diseases include kuru, Gerstmann-Sträussler-Scheinker disease, and fatal familal insomnia. In addition to classic histopathologic methods, the study of prion disease variants has been advanced by the advent of molecular biologic techniques. The clinicopathologic phenotype of sporadic CJD is now known to correlate with the mutation in codon 129. Familial (autosomal dominant) CJD is caused by a mutation in the gene of the prion protein (PrP) and usually affects people younger than 50 years of age. Iatrogenic CJD is caused by the transmission of prions from exposure to contaminated material during surgical procedures. Another mode of transmission involves the ingestion of food, specifically beef products containing the abnormal protein (vCJD).