indicated that a gene for late-onset AD was located on chromosome 19 (Pericak-Vance et al. 1991), in a region that included the APOE gene. Based on these findings, researchers conducted an association study comparing the frequency of three APOE alleles called E2, E3, and E4 in 30 cases and 91 unrelated controls (Strittmatter et al. 1993). The investigators found that whereas all alleles occurred in the controls, the APOE*E4 allele was greatly overrepresented in the AD cases, indicating that this allele is a major risk factor for the development of AD. This robust association between APOE*E4 and AD has been confirmed in many subsequent studies (for a review, see St. George-Hyslop 2000).
