• Jun-Yan Shi, Ping Wang, Bin-Hong Wang, Yong Xu, Xiao Chen, and Hui-Jie Li.
• CAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Psychiatric Hospital of Taiyuan City, Taiyuan 030000, China; Department of Medical Psychology, Shanxi Mental Health Center, Taiyuan 030000, China.
• Neuroscience. 2020 Jun 1; 436: 74-81.

AbstractIndividuals 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.Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

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