The apolipoprotein E ε4 allele (APOE4) is an established risk factor for dementia; however, conflicting findings have been reported as to whether this phenotype confers a heightened risk for late onset depression (LOD) independent of dementia. We examined 2242 persons for incident LOD who also underwent genotyping for APOE4. Major LOD was associated with female sex (odds ratio, 3.61; 95% confidence interval, 1.89-6.90). APOE4 was not associated with major LOD regardless of whether dementia was excluded. In conclusion, we showed that the APOE4 phenotype holds no predictive value for major LOD.