While much of the focus on Alzheimer's disease therapeutics has been directed at beta-amyloid peptide or at cholinergic synaptic transmission, recent data suggest that targeting signal transduction by the amyloid precursor protein (APP) itself may be an alternative approach with significant potential [1]. Here we discuss the possibility that APP-mediated signal transduction, downstream from amyloid-beta peptide production itself, may be an appropriate therapeutic target in Alzheimer's disease.