Brain Homotopic Connectivity in Mild Cognitive Impairment APOE-ε4 Carriers

•Few studies investigated the influence of APOE-ε4 on interhemispheric functional connectivity alterations in MCI.•MCI APOE-ε4 carriers presented increased VMHC in the IFG/insula and MFG/SFG.•MCI APOE-ε4 carriers showed increased seed-based functional connectivity.•The findings provide neuroimaging evidence for the modulation of APOE genotype. Individuals with mild cognitive impairment (MCI) are regarded as being at high risk of developing Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is a well-established genetic risk factor for developing AD. In the present study, by using voxel-mirrored homotopic connectivity (VMHC), we aimed to explore the potential functional disruptions in MCI APOE-ε4 carriers. Resting-state functional magnetic resonance imaging was performed in 35 MCI APOE-ε4 carriers (27 APOE-ε3ε4, 8 APOE-ε4ε4) and 42 MCI APOE-ε4 noncarriers (APOE-ε3ε3). VMHC was employed to investigate the alterations in functional connectivity in MCI APOE-ε4 carriers. We further investigated the seed-based functional connectivity between the VMHC values of altered regions and other brain regions in the two groups. The results showed that MCI APOE-ε4 carriers presented increased VMHC in the inferior frontal gyrus/insula and middle frontal gyrus/superior frontal gyrus in comparison with noncarriers. We found that MCI APOE-ε4 carriers showed increased functional connectivity between the seed regions (bilateral inferior frontal gyri/insula and bilateral middle frontal gyri/superior frontal gyri) and broad brain areas, including the frontal, temporal, parietal, and cerebellar regions. Our findings provide neuroimaging evidence for the modulation of the APOE genotype on the neurodegenerative disease phenotype and may be potentially important for monitoring disease progression in double-high-risk populations of AD.