BACE1 and Alzheimer disease: In addition, rab5 endosome dysfunction can be potentially promoted further by multiple AD-related factors, including increased BACE1 expression and activity,49, 56, 57 inheritance of the ApoE E4 allele,27 lowered Vps3558 and altered handling of cholesterol, which increase BACE1 activity and βCTF levels.59, 60, 61, 62