Background: Cholesterol homeostasis in the brain has been demonstrated in the pathogenesis of Alzheimer's disease (AD). Experimental data support that brain cholesterol turnover can modulate central processes in AD pathogenesis. Excess cholesterol is eliminated from the brain via hydroxylation mediated by cholesterol 24S-hydroxylase (CYP46A1), a main mechanism of maintaining cholesterol homeostasis. The CYP46A1 gene has been suggested as a genetic risk factor for AD. Methods: In this case-control study, we analyzed an intronic CYP46A1 gene single-nucleotide polymorphism (SNP) in 100 AD patients and 80 age-and sex-matched control subjects in the Iranian population. Results: We found a significant difference in CYP46A1 TT-homozygotes genotype (χ 2 = 5.06, df =1, P = 0.02) and T allele frequency