Neurodegeneration in Alzheimer’s disease: caspases and synaptic element interdependence

Neurodegeneration in Alzheimer’s disease: caspases and synaptic element interdependence
Dale E Bredesen

Mol Neurodegener. 2009 Jun 26;4:27.

Extensive genetic, biochemical, and histological evidence has implicated the amyloid-&豪 peptide (A&豪) in Alzheimer’s disease pathogenesis, and several mechanisms have been suggested, such as metal binding, reactive oxygen species production, and membrane pore formation. However, recent evidence argues for an additional role for signaling mediated by the amyloid precursor protein, APP, in part via the caspase cleavage of APP at aspartate 664. Here we review the effects and implications of this cleavage event, and propose a model of Alzheimer’s disease that focuses on the critical nature of this cleavage and its downstream effects.