The biological analysis of nicastrin (NCSTN) shows its crucial role in gamma-cleavage of the amyloid precursor protein. Inhibition of NCSTN demonstrated altered gamma-cleavage activity, suggesting its potential implication in Alzheimer's disease (AD). We sequenced the NCSTN gene promoter region and found two promoter single nucleotide polymorphisms (SNPs) at putative transcription binding sites, -796T/G and -1216C/A. The association study using the promoter SNPs showed no significant genetic effect upon the development of AD. Haplotype analysis with the promoter SNPs and coding SNPs demonstrated no significant difference between familial AD cases and controls. Moreover, the genotype of each promoter SNP did not have an association with age-at-onset in AD. Our investigation suggests that the two promoter SNPs are unrelated to the development of AD, however, further investigation at the promoter region of NCSTN may be necessary to address its potential implication of gene expression in AD.