Sequential cleavage of amyloid precursor protein (APP) by the β-site cleaving enzyme BACE1, which is essential for amyloid β-protein (Aβ) 1–42 and Aβ1–40 biosynthesis, and secretase, initiates the ‘amyloid cascade’ that is central to the pathophysiology of AD (7,8). This evidence concerns the gene BACE1 and Alzheimer disease.