APOE ε4 carriers have thicker cortex in several neocortical areas than ε4 noncarriers (Espeseth T., Westlye L.T., Fjell A.M., Walhovd K.B., Rootwelt H., Reinvang I., 2008. Accelerated age-related cortical thinning in healthy carriers of apolipoprotein E ε4. Neurobiol. Aging 29, 329-340). To investigate potential physiological and cognitive correlates of these anatomical effects structural magnetic resonance imaging (MRI) data were obtained from 20 APOE ε3 homozygotes and 20 ε4 hetero- and homozygotes, and event-related potentials (ERPs) were recorded during a selective attention task (i.e. three-stimulus oddball). Several areas in both hemispheres were thicker in ε4 carriers than in noncarriers. ε4 carriers also had lower amplitudes to distractors (P3a) and lower target detection accuracy than noncarriers. Mean thickness in cortical areas were correlated with P3a amplitudes, which in turn correlated with accuracy. Path analyses showed that APOE-related difference in accuracy was mediated by APOE-related differences in cortical thickness and P3a amplitudes. The results suggest that APOE ε4 modulates the structural integrity of critical nodes in brain attentional networks.