The amyloid-bpeptide (Ab) is the principal component of the senile plaques found in the brains of patients with Alzheimer’s disease (AD). It is produced from the Ab precursor protein (APP) cleaved consecutively by bsecretase and g-secretase [reviewed in Vassar and Citron, 2000]. The gene for b-secretase, also referred to as b-site APP cleaving enzyme, or BACE1, is located on chromosome 11q23. 3 [Hussain et al., 1999; Sinha et al., 1999; Vassar et al., 1999; Yan et al., 1999; Lin et al., 2000]. As a genetically heterogeneous neurodegenerative disorder with familial and sporadic forms, mutations in APP gene, presenilin 1 gene, and presenilin 2 gene account for 30–40% of the rare early-onset familial AD [Blacker and Tanzi, 1998], while for the more common sporadic AD, the e4 allele of the apolipoprotein E (APOE) gene has been found to be the only major risk factor [Poirier et al., 1993; Saunders et al., 1993; Strittmatter et al., 1993]. However, about 50% of lateonset AD cases do not carry any APOEe4 allele