Traditionally, in the context of Alzheimer's disease, the apolipoprotein E epsilon 2 (APOE epsilon 2) allele is a protective factor and the APOE epsilon 4 allele is a destructive factor. However, this inverse relationship has recently been challenged, and the neural mechanisms underlying the effects of APOE genotype on Alzheimer's disease remain unclear. A resting-state functional magnetic resonance imaging study was conducted to investigate the effects of APOE genotype and age on amygdala functional connectivity (AFC) networks in 84 patients with amnestic mild cognitive impairment and 124 cognitively normal order adults. The results indicated that the APOE epsilon 2 and APOE epsilon 4 alleles produced convergent effects in the right AFC network but divergent effects in the left AFC network. As age increased, APOE epsilon 2 carriers showed stable AFC, whereas APOE epsilon 4 carriers exhibited decreased AFC in all participants. Furthermore, mediation analysis revealed that connectivity strength regulates the effects of APOE genotype and age on cognitive function in amnestic mild cognitive impairment patients. Our findings suggest that the APOE epsilon 2 and APOE epsilon 4 alleles produce both convergent and divergent topological effects on brain function. (C) 2017 Elsevier Inc. All rights reserved.