BACE1 and Alzheimer disease: The discovery that an A673T (Icelandic) mutation in APP at the P2′ residue of the BACE1 cleavage site reduces BACE1 cleavage of APP and protects against both AD and other age-related cognitive decline [14] provides further strong support for the hypothesis that Aβ production - and specifically BACE1 cleavage - is a critical event in AD pathogenesis.