Apolipoprotein E (APOE) epsilon4 allele is a major risk factor for the development of Alzheimer's disease (AD). It has been suggested that the quantitative expression of APOE alleles results from mutations in the promoter region of this gene. We studied the -491A/T promoter polymorphism and whether it is dependent on the APOE epsilon4 allele in clinic-based AD (n = 106) and community-based control (n = 123) samples. The -491A/T and APOE polymorphisms were analyzed using the polymerase chain reaction method and restriction fragment length polymorphism analysis. The APOE epsilon4 allele was strongly associated with AD when compared with controls, P < 0.001 (odds ratio 5.85, 95% CI 3.29- 10. 41). The genotype distribution of the -491A/T polymorphism did not significantly differ between the study groups (P = 0.063), and the -491A allele was not associated with any significant risk in the AD group when compared to controls (odds ratio 1.82, 95% CI 0.95-3.49). However, haplotype estimation analysis indicated linkage disequilibrium between APOE -491A/T polymorphism and the APOE epsilon4 allele. Our findings confirm APOE polymorphism still to be the most efficient predictor of risk in AD.