In the Japanese population, sporadic late-onset Alzheimer's disease (LOAD) cases had significantly higher frequencies of the A allele of alpha 1-antichymotrypsin (ACT) gene as well as the epsilon 4 allele of apolipoprotein E (APOE) gene than controls. The odds ratio for LOAD in APOE4 carriers with the ACT-A allele was more than six times that in APOE4 carriers without the ACT-A allele (21.1 vs 3.2). These results indicate that the ACT-A allele is a risk modifier for LOAD in APOE4 carriers.