If the transient iAβ depletion therapy via its targeted degradation by Aβ-cleaving activities of BACE1 and/or BACE2 or by any other suitable iAβ-depleting agent were implemented at an early symptomatic stage of AD, the progression of the disease in the early-affected brain compartment (e.g., panel A of Figure 14) would cease, and the AD pathology would not occur, due to iAβ depletion, in other brain compartments where it did not yet commence or progressed only insignificantly. This evidence concerns the gene BACE2 and Alzheimer disease.