Given this capability, the design of the human neuronal cell-based model of AD is obvious: activate the AβPP-independent iAβ production pathway and ascertain that it is self-sustaining, i.e., that the AD Engine is operative, and the cellular AD pathology would follow; the activity of the AβPP-independent iAβ generation pathway can be assessed as described in Section 12 below. This evidence concerns the gene APP and Alzheimer disease.