A functional polymorphism of mitochondrial aldehyde dehydrogenase gene (ALDH2 1/2 polymorphism) can influence the accumulation of acetaldehyde which may have a role in Alzheimer's disease (AD), and is widely prevalent among Mongoloids. Therefore ALDH2 1/2 polymorphism may represent a good candidate for genetic risk factors for AD, especially in East Asian. A case-control study from Japan found that ALDH2*2 was associated with late-onset AD (LOAD), interacting synergistically with the presence of the apolipoprotein E allele 4 (APOE epsilon4). But the subsequent studies in Koreans didn't find the similar result. To determine whether the ALDH2 gene 1/2 polymorphism contributes to the risk for LOAD in Chinese, we have investigated 188 sporadic LOAD patients and 223 healthy controls from Chinese. A significantly increased risk of AD in the carriers of ALDH2*2 allele (OR=3.11, 95% CI 2.06-4.69, P<0.001) was observed. After stratifying by APOE epsilon4 status, increased LOAD risks associated with the ALDH2 2 allele carriers only in the APOE epsilon4 non-carriers (chi2=31.79, df=1, P<0.001) and with the 2-allele in either groups (chi2=6.64 df=1, P=0.0099 and chi2=37.38, df=1, P<0.001) were seen. These results suggested that the ALDH2 gene 1/2 polymorphism might be a risk factor for LOAD and dependent on APOE epsilon4 status in Chinese.