In a previous study, we reported that Alzheimer disease (AD) patients with an apolipoprotein E (APOE) epsilon 4 allele (+ APOE4) show more severe loss of nucleus basalis (NB) cholinergic cells than patients without epsilon 4 alleles (-APOE4). The present study investigates the effects of a single oral administration of THA 25 or 50 mg on cortical spectral EEG activity in + (five APOE4/4, six APOE4/3) and -APOE4 (eight APOE3/3) AD patients. THA 25 mg had no significant effect on EEG activity in any AD patients. However, THA 50 mg increased alpha activity and alpha/theta ratio in -APOE4 patients. In contrast, THA 50 mg had no effect on EEG activity in + APOE4 patients. This result tentatively suggests that in AD patients APOE genotype may affect the response of cortical electrical arousal to cholinergic therapy that enhances the efficacy of presynaptic NB axons.