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Apolipoprotein E (ApoE) plays a vital role in cholesterol metabolism and its allele polymorphisms have been associated with several diseases including Alzheimer’s disease (AD). There are few systematic studies on ApoE polymorphism and its association with AD in Chinese population. To examine this issue, participants included 4251 subjects and 404 AD patients with 390 healthy elderly residing in Chongqing city were genotyped. The results showed that the 3 allele presented the highest frequency (82%), followed by 4 (6.25%) and 2 (11.75%) in general population. 3/3 genotype carriers are the most common ones (64.19%) and the 4/4 had the lowest frequency (0.59%). The frequency of ApoE4 allele frequency in AD (15.35%) was significantly higher than control (10.00%). Those carriers of two 4 allele have five time higher risk to develop AD. Our study demonstrate that ApoE4 allele is a risk factor of AD for Chinese population.