It is intriguing to observe a variant within the FOXO3 locus is linked to AD risk, considering consistent evidence linking FOXO3 to longevity in animal models and human samples.33,34 Given the result's incongruence among 8 other null findings for IGF-determining variants, pleiotropic effects may link FOXO3 function with AD independently of FOXO3 effects on IGFs. This evidence concerns the gene FOXO3 and Alzheimer disease.