A genetic polymorphism in intron 13 of the FE65 gene (APBB1) was reported to be associated with Alzheimer's disease (AD). Our analyses of this polymorphism, both in a family-based or a case-control sample, fail to support the association between the FE65 intron 13 polymorphism and AD. We performed the sibship disequilibrium test (SDT, P=0.77) and the sib transmission/disequilibrium test (Sib-TDT, P=0.56) in a family-based study which included 526 subjects from 158 sibships. In addition, we compared the genotype and allele frequencies of this biallelic polymorphism in 311 AD patients to those of a control group consisting of 260 subjects and found no significant difference (chi(2), P=0.847 and P=0.586, respectively). Furthermore, our two-point linkage analysis in a family-based sample was in agreement with a genome wide scan for linkage to AD and showed no evidence for linkage to the short arm of chromosome 11 where the FE65 gene is located. We conclude that the association of the FE65 intron 13 polymorphism with AD, if any, is smaller than previously reported.