[Creutzfeldt-Jakob disease]

Abstract

Creutzfeldt-Jakob's disease is a transmissible encephalopathy manifesting with dementia and motor disturbances, which usually progresses rapidly and is lethal within months. It occurs mainly sporadically, but it can also be transmitted by proteinaceous infective particles called prions. The diagnosis has to rely on clinical symptoms, EEG and brain biopsy being the most suitable additional examinations. No therapy is yet known. "Naturally" occurring transmission has not been observed: all transmitted cases reported so far have been iatrogenic and followed administration of cadaveric hypophyseal hormones, transplantation of tissue from CNS or related organs, or brain surgery with contaminated instruments. Remarkable discoveries in the past decades with respect to the molecular and genetic characterization of the transmissible pathogen have led to a new understanding of the disease. The infective agent appears to be an abnormal isoform of a physiologically occurring protein: the cellular prion (PrPc). The crucial pathogenetic event is the conformational conversion of PrPc into its pathological isoform (PrPsc), an event thought to be triggered autocatalytically by the infectious agent itself. The disease can be elicited in experimental animals by inoculation of PrPsc. In the sporadic cases of Creutzfeldt-Jakob's disease, PrPsc is thought to arise through spontaneous conversion of PrPc. A growing body of evidence indicates that specific alleles of the prion gene confer a genetic predisposition to Creutzfeldt-Jakob's disease and to related pathologies.