Reduced hippocampal activity during encoding in cognitively normal adults carrying the APOE ɛ4 allele

► Older cognitively normal APOE ɛ4 carriers showed less activation than non-carriers in the hippocampus proper during encoding. ► Specifically, spatial encoding was contrasted against the dot-control task, a visually engaging non-MTL dependent control, encoding-related activation was significantly lower in carriers than non-carriers. ► No ɛ4-related differences in the hippocampus were found when spatial encoding was compared with fixation. ► Lower activation was not global since encoding-related activation in early visual cortex (left lingual gyrus) was not different between APOE ɛ4 carriers and non-carriers. ► The present study further highlights the role of low-level control tasks to tease apart the influence of genetic susceptibilities on brain activity during learning, particularly in cognitively normal middle-aged to older adults.