Fibroblast growth factor I (FGF1, also known as acidic FGF) protects selective neuronal populations against neurotoxic effects such as those in Alzheimer's disease (AD) and HIV encephalitis. The FGF1 gene is therefore a strong candidate gene for AD. Using the promoter polymorphism of the FGF1 gene, we examined the relationship between AD and the FGF1 and apolipoprotein E (APOE) genes in 100 Japanese autopsy-confirmed late-onset AD patients and 106 age-matched non-demented controls. The promoter polymorphism (-1385 A/G) was significantly associated with AD risk. The odds ratio for AD associated with the GG vs non-GG genotype was 2.02 (95% CI = 1.16-3.52), while that of epsilon4 vs non-epsilon4 in APOE4 gene was 5.19 (95% CI = 2.68-10.1). The odds ratio for APOEepsilon4 and FGF1 GG carriers was 20.5 (95% CI = 6.88-60.9). The results showed that the FGF1 gene is associated with autopsy-confirmed AD. (C) 2004 Elsevier Inc. All rights reserved.