Association of the APOE ε4 allele with clinical subtypes of late life depression

The APOE genotypes of 45 elderly inpatients with major depression were determined to investigate the relationship of this disorder to irreversible dementia in late life. We specifically tested the hypothesis that the frequency of the APOE ε4 allele is elevated in depressed elders with cognitive impairment or psychotic features, subtypes that have been reported to be at increased risk of developing Alzheimerʹs disease (AD). The frequency of ε4 allele was not elevated in the overall group of 45 inpatients and, contrary to our expectation, was not associated with cognitive impairment in this group. In contrast, the ε4 allele frequency for the patients with psychotic features was nearly four times that for the patients without psychotic features and nearly double that of elderly controls. These data suggest that elderly depressed inpatients with cognitive impairment are at risk for developing AD by an ε4-independent pathway, while those with psychotic features are at risk for developing AD by an ε4-dependent pathway. These findings suggest that subtypes of idiopathic major depression in late life may serve as landmarks that distinguish separable pathogenetic pathways to AD.