APP and Alzheimer disease: Second, the suppression of the proteolytic cleavage of AβPP by BACE1 and, consequently, a substantial inhibition of the production of Aβ had no beneficial effect on the progression of the disease, implying that AD pathology-driving iAβ is produced in the AβPP-independent pathway [1,2,3,4,5,6,7,8,9].