BACE1 and Alzheimer disease: Although BACE1 mutations have not yet been linked to AD risk, genetic variants surrounding the β-secretase site in the APP (including the Swedish mutation KM/NL, the Italian variant A673V, and the A673T) are associated with either higher or lower affinity for BACE1 to initiate APP cleavage, thus exerting a protective or risk effect, respectively [3].