BACE1 and Alzheimer disease: And, as discussed below, in mice and monkeys with DIO/MetS/T2DM, we found that hyperinsulinemia provokes increases in activity of β‐site amyloid precursor protein (β‐APP) cleaving enzyme‐1 (BACE1), which, in brain, increases Aβ‐peptide production and may abet development of Aβ‐plaques and phospho‐tau “tangles”15 in AD, which alarmingly afflicts one of five women and one in 10 men over age 65, and one of two humans over age 85.