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Increasing age and carrying an APOEε4 allele are well established risk factors for Alzheimer's disease (AD). The earlier age of onset of AD observed in ε4-carriers may reflect an accelerated aging process. We recently reported that APOE genotype modulates brain function decades before the appearance of any cognitive or clinical symptoms. Here we test the hypothesis that APOE influences brain aging by comparing healthy ε4-carriers and non-carriers, using the same imaging protocol in distinct groups of younger and older healthy volunteers. A cross-sectional factorial design was used to examine the effects of age and APOE genotype, and their interaction, on fMRI activation during an encoding memory task. The younger (N=36; age range 20–35; 18 ε4-carriers) and older (35 middle-age/elderly; age range 50–78years; 15 ε4-carriers) healthy volunteers taking part in the study were cognitively normal. We found …