The rationale for the depletion of iAβ as therapeutic strategy for AD is no less apparent: reduce levels of iAβ below those causing AD pathology and the progression of the disease would stop; deplete iAβ to levels below the T1 threshold and the AβPP-independent iAβ generation pathway would be rendered unsustainable and inoperative (unless supported unconventionally). The gene discussed is APP; the disease is Alzheimer disease.