Interactive Effect of Apolipoprotein E Genotype and Age on Hippocampal Activation During Memory Processing in Healthy Adults

Although the apolipoprotein E (APOE) ...4 allele is a major genetic risk factor for late-onset Alzheimer disease, its effect on hippocampal function during episodic memory is controversial because studies have yielded mixed results. The age of the studied cohorts may contribute to this apparent inconsistency: activation for ...4 carriers tends to be increased in studies of older adults but decreased in some studies of younger adults. Consistent with differential age effects, research in transgenic mice suggests that the ...4 allele may particularly affect the aging process. To define the interactions of age and this allelic variation on brain activation during episodic memory across adult life in healthy individuals. Functional magnetic resonance imaging (fMRI) using an episodic memory paradigm to test for differences in neuroactivation across APOE genotypes and age groups. A federal research institute. Healthy white volunteers (APOE ...3 homozygotes and ...2 and ...4 heterozygotes) completed the fMRI task (133 volunteers aged 19-77 years). Memory-related regional blood oxygenation level-dependent (BOLD) activation. Genotype affected the pattern of change in hippocampal BOLD activation across the adult lifespan: older age was associated with decreased activation in ...2 carriers and, to a lesser extent, in ...3 homozygotes, but this pattern was not observed in ...4 carriers. Among young participants, ...4 carriers had less hippocampal activation compared with ...3 homozygotes despite similar task performance. The findings support the hypothesis that aging and APOE allele status have interacting effects on the neural substrate of episodic memory and lend clarification to disparities in the literature. The stepwise decrease in activation with age found among genotype groups resembles the order of susceptibility to Alzheimer disease, suggesting a compensatory neurobiological mechanism in older asymptomatic ...4 carriers. (ProQuest: ... denotes formulae/symbols omitted.)