ABSTRACT
The prion diseases (PrD) are a group of unusual neurodegenerative disorders that affect both humans and animals, are associated with a variety of phenotypes, and are transmissible. The earliest description of PrD was that of Creutzfeldt and then Jakob in the early 1900s (1,2) as a progressive dementia associated with gait abnormalities and extensive vacuolation and astrocytic gliosis on pathologic review of the brain. In the mid-1950s, while studying primitive cultures in the Highlands of New Guinea, Carleton Gajdusek recognized and described a disease the Fore people, living in this region, called “kuru.” Sufferers of kuru developed a progressive gait ataxia, unusual behavior, and a relatively rapid progression to death. Gajdusek’s studies suggested that this disease was the result of a transmissible agent carried within the brain of the affected individual that was horizontally transmitted rituals that involved cannibalism. Women and children were most affected by the disease, due likely to their greater contact with infectious tissue during both the preparation of the feast and the ritualistic ceremony. Pathologic examination of the kuru brain revealed the same pattern of vacuolation (also called spongiform change) that was observed in the disease described by Creutzfeldt and Jakob. Most importantly, however, this same pathology was astutely recognized by the veterinarian William Hadlow as the same pathology present in scrapie, a known transmissible disease of sheep associated with similar features of gait dysfunction, behavioral changes, and a rapid progression to death. It was natural to speculate that CJD (Creutzfeldt-Jakob disease) and kuru were similarly transmissible, which was confirmed in the mid-1960s (3,4). These results led
to the recognition of several other transmissible spongiform encephalopathies (TSEs). Until relatively recently, the infectious agent of the TSEs was considered to be a slow virus (5), yet despite considerable effort, evidence for a virus has not materialized. Instead, a wealth of data has accumulated to implicate an abnormal isoform of the prion protein (PrP) as the etiologic agent in these diseases (6). Several years after Gajdusek received the first Nobel Prize for linking the transmissible nature of these diseases, Stanley Prusiner captured the second TSE-related Nobel Prize for his discovery of the prion, the infectious protein of PrD.
