["There is a recognized but poorly understood relationship between late-life depression (LLD) and progressive dementia. Both cognitive impairment co-occurring with LLD and a late age-of-onset of first lifetime depressive episode appear to be associated with subsequent progressive dementia. A history of major depression, especially when the first onset occurs in late-life, has been identified as a risk factor for Alzheimer's disease (AD). The major genetic risk factor for sporadic AD is carrying one or more apolipoprotein E4 (APOE4) alleles. We hypothesized that the association between LLD and dementia risk would be mediated by APOE4, specifically that APOE4 allele frequency would be associated with cognitive impairment and later age-of-depression-onset. We also predicted that APOE4 allele frequency would be increased among subjects with LLD.", 'We compared the distribution of APOE2, APOE3, and APOE4 alleles in groups of LLD (n=160), AD (n=568) and elderly control (EC; n=156) subjects.', 'The allele distribution of the cognitively impaired LLD subgroup was not different from either the cognitively normal subgroup or the EC group but was different from the AD group. However, mean age-of-onset of depression in APOE4 carriers (51.4+/-20.7) was significantly lower than non-carriers (58.8+/-16.8). The allele distribution in LLD overall was significantly different from the AD but not the EC group.'] Is aPOE associated with age-of-onset , but not cognitive functioning , in late-life depression?