APP and Alzheimer disease: Despite significant progress in the AD genetics, including the identification of three genes (PSEN1, PSEN2, and APP) [2,3,4] that cause familial AD, the discovery of APOE as a major risk factor [5,6] and the identification of over 30 other genes with smaller but significant contributions [7,8,9,10], the etiological treatments currently approved have not shown substantial improvements in managing the disease progress.