Neural precursor cell-expressed, developmentally downregulated 9 (NEDD9) has been suspected to be associated with Alzheimer's disease (AD) through participating in the formation of neurite-like membrane extensions and neurite outgrowth to affect the number of neuronal cells/synapses in the brain under stressful conditions. A recent large-scale, multi-tiered association study has identified significant association of a common single nucleotide polymorphism (SNP) rs760678 in the NEDD9 gene with predisposition to late-onset Alzheimer's disease (LOAD) in Caucasians. In order to evaluate the involvement of the NEDD9 polymorphism in the risk of sporadic LOAD, we performed an independent case-control association study to analyze the genotype and allele distributions of the NEDD9 rs760678 polymorphism in a Han Chinese population (383 LOAD cases and 369 healthy controls). There were significant differences in genotype and allele frequencies between LOAD cases and controls (genotype P=0.003, allele P=0.002). After stratification by APOE ε4-carrying status, the C allele of rs760678 was only significantly associated with LOAD in non-APOE ε4 allele carriers (OR=1.43, 95%, CI=1.06-1.94, P=0.024). In addition, a logistic regression analysis also conferred positive association between the SNP rs760678 and LOAD (dominant model: OR=2.10, 95% CI=1.23-3.58, P=0.007; additive model: OR=1.37, 95% CI=1.09-1.74, P=0.008) after adjustment for age, gender, and the APOE ε4 carrier status. The study demonstrated a significant association between the tested SNP and LOAD, indicating that NEDD9 polymorphism has a possible role in changing the genetic susceptibility to LOAD in a Han Chinese population. Copyright © 2010 Elsevier B.V. All rights reserved.