AimTo investigate the influence of apolipoprotein E (APOE) genotype on cortical activity, using the event-related potential P300 in healthy older adults and individuals with Alzheimer’s disease (AD). MethodsA cohort of 37 healthy older adults and 48 with AD participated in this study and completed an auditory oddball task using electroencephalographic equipment with 21 channels (10–20 system). APOE genotyping was obtained by real-time PCR. ResultsAD presented increased P300 latency and lower P300 amplitude, compared to healthy older adults. AD APOE ε4 carriers presented increased P300 latency in F3 (420.7 ± 65.8 ms), F4 (412.0 ± 49.0 ms), C4 (413.0 ± 41.1 ms) and P3 (420.4 ± 55.7 ms) compared to non-carriers (F3 = 382.5 ± 56.8 ms, p < 0.01; F4 = 372.2 ± 56.7 ms, p < 0.01; C4 = 374.2 ± 51.7 ms, p < 0.01; P3 = 384.4 ± 44.4 ms, p < 0.01). Healthy older adults APOE ε4 carriers presented lower Fz amplitude (2.6 ± 1.5 μV) compared to non-carriers (4.9 ± 2.9 μV; p = 0.02). Linear regression analysis showed that being a carrier of APOE ε4 allele remained significantly associated with P300 latency even after adjusting for sex, age, and cognitive grouping. APOE ε4 allele increases P300 latency (95% CI 0.11–0.98; p = 0.02). ConclusionAPOE ε4 allele negatively impacts cortical activity in both healthy older adults and AD individuals.