The history of prion diseases is derived from descriptions of scrapie of sheep and goats in the eighteenth century. In 1920, Creutzfeldt-Jakob disease was reported as the first case of human prion diseases, which was recognized as subacute spongiform encephalopathy, one of neurodegenerative diseases. Afterwards, many transmission experiments were performed, which lead to the establishment of the fundamental concept, transmissible spongiform encephalopathy(TSE). The infectious agent was supposed to be a novel virus, so TSE was classified into slow virus infection. In 1982, Prusiner investigated the infectious fraction of scrapie-infected brain homogenate, defined the infectious agent as proteinaceous infectious particles that resist inactivation by procedures that modify nucleic acid and newly designated as prion after virion in viral infection.