EVOLUTION OF A STRAIN OF CJD THAT INDUCES BSE-LIKE PLAQUES

Bovine spongiform encephalopathy (BSE) has become a public health issu e because a recently evolved BSE agent has infected people, yielding a n unusual form of Creutzfeld-Jakob disease (CJD). A new CJD agent that provokes similar amyloid plaques and cerebellar pathology was seriall y propagated. First-passage rats showed obvious clinical signs and act ivated microglia but had negligible PrP-res (the more protease-resista nt form of host PrP) or cerebellar lesions. Microglia and astrocytes m ay participate in strain selection because the agent evolved, stabiliz ed, and reproducibly provoked BSE-like disease in subsequent passages. Early vacuolar change involving activated microglia and astrocytes pr eceded significant PrP-res accumulation by more than 50 days. These st udies reveal several inflammatory host reactions to an exogenous agent .