Apoptosis and dendritic dysfunction precede prion protein accumulation in 87V scrapie

The sequence of events involved in the neurodegeneration caused by transmis sible spongiform encephalopathies (TSEs) is not yet known. Using a murine s crapie model in which neurodegeneration in the hippocampus is restricted to CA2, we show that pyramidal neuron damage and death by an apoptotic mechan ism occur early in the incubation period, prior to the appearance of CA2 di sease-specific accumulation of PrP and the onset of clinical disease. We su ggest that the initial hippocampal pathological event in this model is dend ritic dysfunction and activation of an apoptotic pathway rather than PrP ac cumulation. NeuroReport 12:2147-2153 (C) 2001 Lippincott Williams & Wilkins .