Genetic, biochemical, and behavioral studies suggest that pathologic generation of the neurotoxic Aβ peptide from sequential APP proteolysis is the crucial step in the development of AD, and APP is metabolized in a rapid and highly complex fashion by a series of sequential secretases, including β-secretases (BACE1), γ-secretase (γ-SC) and the ADAM family as α-secretases2. The gene discussed is APP; the disease is Alzheimer disease.