BACE1 and Alzheimer disease: Now that all BACE1 inhibitor programs in symptomatic and prodromal AD have ended in failure (Imbimbo and Watling, 2019; McDade et al., 2021; Bazzari and Bazzari, 2022), trials need to shift to target the earlier preclinical stage across the AD spectrum such as secondary prevention (presymptomatic populations) and primary prevention [before Aβ build-up preceding symptom onset by ~15 years (Bateman et al., 2012)] (Figure 1).