BACE1 and Alzheimer disease: Although homozygous BACE1 knock-out mice develop certain phenotypic abnormalities including reduced body size, hyperactive behavior, decreased grip strength and elevated pain sensitivity [12–14], probably because the cleavage of other BACE1 substrates such as neuregulin 1 [13, 14] and β-subunits of voltage-gated sodium channels [15] is blocked, BACE1 heterozygous knockout mice do not develop such abnormal phenotypes and heterozygous knockout of BACE1 still can reduce Aβ deposition in AD mice [16, 17].