BACE1 and Alzheimer disease: For example, a recently concluded randomized clinical trial with an inhibitor of β-secretase (BACE1), the enzyme that cleaves APP to uncover the N-terminus domain of Aβ1-42, did not show any reduction in cognitive or functional decline in AD patients, suggesting that either disease progression does not rely exclusively on amyloid formation or, alternatively, that anti-amyloid drugs should be administered several years prior to the onset of AD to be effective (Egan et al., 2018).