To investigate the effect of single nucleotide polymorphisms (SNPs) of the upstream stimulatory factor (USF) 1 and 2 genes on the onset of Alzheimer's disease (AD), a case-control study was performed. The SNPs were genotyped by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 236 AD patients and 120 age-matched controls of Japanese descent. We observed no significant association between the three SNPs of the USF 1 gene and AD in our Japanese participants. In addition, the SNPs studied did not affect plasma cholesterol levels in our AD cases. For the USF 2 gene, the two SNPs did not show significant association with onset of AD. Our study suggests that the three SNPs of the USF 1 gene and two SNPs of the USF 2 gene presented here are not associated with onset of AD.