Increased BACE1 levels and activities have been shown in AD brains (Fukumoto et al., 2002; Yang et al., 2003; Li et al., 2004), with a further increase in cerebrospinal fluid (CSF) or brains of AD subjects with ApoE4 (Stockley et al., 2006; Ewers et al., 2008). Here, APOE is linked to Alzheimer disease.