Whereas this review is focused on BACE1 inhibitors whose efficacy in rescuing ALF has been demonstrated in asymptomatic AD mouse models (Ohno, 2021), ALF assessment is expected to provide a great opportunity to sensitively evaluate other Aβ-reducing interventions such as γ-secretase modulators in a long preclinical phase of AD continuum. This evidence concerns the gene BACE1 and Alzheimer disease.