The ability to regulate the activity of the AβPP-independent iAβ generation pathway and, even more importantly, to control the formation of NFTs via BACE-mediated iAβ depletion would constitute a proof of principle for the utilization of BACE activators (or other iAβ-depleting agents) as potential AD drugs and would justify a major effort to develop such agents. Here, APP is linked to Alzheimer disease.