Activation of the amyloid cascade by intracerebroventricular injection of the protease inhibitor phosphoramidon

We presently investigated the pathological effects of prolonged inhibition of brain β-amyloid (Aβ) degradation in vivo. The results obtained revealed that intracerebroventricular injection of the protease inhibitor phosphoramidon into wild-type mice for up to a month elevated the soluble and deposited brain Aβ levels and concomitantly induced the neurodegeneration of distinct hippocampal neurons as well as neuroinflammation. These findings reproduce pathological effects associated with the initial stages of the amyloid cascade and provide a novel model system for studying their underlying mechanisms.