Alzheimer’s disease (AD) is a common, degenerative form of dementia characterized by the accumulation of plaques containing amyloid β-peptides (Aβ). Nicastrin (NCSTN) is a type I trans-membrane glycoprotein and an essential component of γ-secretase, a multiprotein complex required for the production of the mature form of Aβ. Overexpression of wild-type NCSTN increases Aβ production, indicating that the strict regulation of NCSTN expression may play a fundamental role in the pathogenesis of AD. In this study we investigated the effect of a single-nucleotide polymorphism (SNP; rs10752637), located in the promoter region of the NCSTN gene, on NCSTN promoter activity. First, the rs10752637 genotypes were determined in a Chinese population consisting of 462 patients with sporadic AD and 470 normal control subjects. The distributions of the rs10752637 genotypes and allele frequencies were significantly different between the AD and control groups, with the -922T allele significantly associated with the occurrence of AD. Reporter assays indicated that the rs10752637 -922T allele had a significantly increased promoter activity relative to the -922G allele. Furthermore, gel shift assays demonstrated that the -922T allele preferentially bound to components of nuclear extracts. Overall, our results indicate that the rs10752637 SNP can likely influence the expression of NCSTN, and that this may be an influencing factor during the pathogenesis of AD.