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Epsilon 4 allele of apolipoprotein E (APOE-ɛ4) is a major risk factor for Alzheimer's disease (AD). The association of APOE allele frequencies with AD remains unknown in developing countries. We examined the frequency of APOE alleles in 105 patients with AD and 129 cognitively normal subjects of similar age and sex (control group), in Tehran, Iran. The APOE-ɛ4 allele frequency was significantly higher in the AD subjects than in the control group (21% versus 6.2%, p<0.001). In addition, the OR for APOE-ɛ4 heterozygous and homozygous subjects were 3.2 (p=0.001) and 12.75 (p=0.01), respectively. The OR was not uniform across age groups. The AD subjects carrying one or two APOE-ɛ4 allele showed earlier age-at-onset (p<0.001). These data suggest that the APOE-ɛ4 allele increase the risk for AD in Tehran population in a dose and age-dependent manner. Although the APOE-ɛ2 allele frequency was …