There is compelling evidence indicating that reduction of high-density lipoprotein (HDL) level is associated with increased risk of Alzheimer's disease (AD). It is known that the levels of HDL are regulated by cholesteryl ester transfer protein (CETP) and several single nucleotide polymorphisms (SNPs) in the CETP gene have been shown to be associated with the levels of HDL. Therefore, it is assumed that the CETP gene is a reasonable candidate for modifying the susceptibility in AD. In the present study, we investigated the association of four CETP SNPs (D442G, L296Q, Taq1B and I405V) with the risk for sporadic AD in Northern Han-Chinese. One hundred and seven AD cases and 115 age and gender-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. The frequency of DG genotype (P=0.035) or G allele (P=0.038) for the CETP (D442G) polymorphism was greater in control subjects than in AD patients. The age- and sex-adjusted odds radio for DG vs. DD genotype was 0.202 (95% CI 0.043-0.958, P=0.044). When the sample was stratified by APOE epsilon4 carrier status, the same tendency (P=0.042 for DG genotype, P=0.046 for G allele) was observed in the presence of APOE epsilon4, but not in the absence of APOE epsilon4 (P=0.284 for DG genotype, P=0.298 for G allele). However, these results became not statistically significant after correcting for multiple testing (Bonferroni) because of limited number of our sample. Our current results suggest that G allele of CETP D442G may have a potential protective effect against the development of AD, especially in APOE epsilon4 carriers, in Northern Han-Chinese, possibly through regulating the HDL level in the brain.