<p>Background: Alzheimer&#39;s Disease (AD) is a neurodegenerative disorder, which is the most common cause of dementia in the elderly. Accumulation of &beta;-amyloid plaques outside neurons is the most important pathological hallmark of AD, which is produced by cleavage of amyloid precursor protein by the Alzheimer&#39;s &beta;-secretase (<em>BACE1</em>). Since&nbsp;<em>BACE1 </em>is a key enzyme in the formation of &beta;-amyloid peptides, the purpose of this study was to assess the association between polymorphisms of G/C (rs638405) <em>BACE1</em> gene with sporadic AD in Khuzestan, Isfahan and Fars provinces in Iran.<br /> Methods: Genotypes were determined by the PCR&ndash;Restriction Fragment Length Polymorphism (PCR&ndash;RFLP) technique in two groups including 89 sporadic AD patients and 73 healthy subjects.<br /> Results: The findings of the <em>BACE1</em> G/C (rs638405) polymorphism revealed that there was no significant difference between AD patients and controls in men group; however, there was a weak difference in the frequency of CC genotype between patients and controls in women group (<em>&chi;</em>²=3.333, df=1, p=0.068).<br /> Conclusion: The results of this study suggest that the G/C (rs638405) polymorphism of BACE1 gene might not be related with sporadic AD in Khuzestan, Isfahan and Fars provinces in Iran. However, our results do not support a genetic risk factor of this polymorphism for developing AD in male group of this study.</p>