Prion diseases

Abstract

The human prion diseases are a diverse group of neurodegenerative diseases that are classified by several criteria including disease etiology, PRNP polymorphisms at codon 129, PrPSc types and subtypes, prion incubation period and disease duration, clinical presentation and neuropathology. Creutzfeldt-Jakob disease (CJD) is unique in that it can have a sporadic, inherited, and infectious etiology, and all three forms can subsequently be transmitted following experimental inoculation of brain tissue. PrPSc is an unusual pathogen that fails to induce a prion-specific host immune response, but PrPSc-induced damage to the brain likely causes a proinflammatory response that contributes to neurodegeneration. The human prion diseases are primarily localized to the nervous system, but variant CJD (vCJD) also has a peripheral distribution in secondary lymphoid tissues that is consistent with oral exposure to bovine spongiform encephalopathy (BSE). The prion agent uses the immune system for targeting to lymphoid organs, agent replication, and neuroinvasion through fibers that innervate lymphoid tissues. In chronic inflammatory conditions in which lymphoid organogenesis can occur in non-lymphoid tissues, ectopic peripheral prion infection can be established and could play a role in prion transmission.