Resolving the relationship between ApolipoproteinE and depression.

Several studies have reported an association between the ApolipoproteinE-epsilon4 (APOE4) allele and depression among elders. However others have failed to find an association. Since APOE4 is a well recognized risk factor for Alzheimer dementia, cognitive status may represent an important confounder between APOE4 and depression. In this investigation, we examined the relationship between the ApolipoproteinE-epsilon4 allele and depression among elders accounting for cognitive status. Using a case-control design (n=1052), we investigated the association between ApolipoproteinE-epsilon4 and depression in Alzheimer disease patients (n=528) and in cognitively intact controls (n=524). We demonstrated an apparent association between the APOE4 allele and depression in the combined dataset (p=0.001) when not controlling for cognitive status. However, once stratified by the presence of Alzheimer disease, there was no association in either the Alzheimer group (p=0.290) or the cognitively intact controls (p=0.494). In this dataset there is no association between the ApolipoproteinE-epsilon4 allele and depression among those with Alzheimer disease or among cognitively intact elders. However there is a significant association between female gender and depression in the cognitively intact (p=0.003) but not among those with Alzheimer disease. Additionally, individuals with Alzheimer disease and depression had a significantly younger age of onset for their Alzheimer disease than those without depression (p=0.017).