Shi Jun-Yan, Wang Ping, Wang Bin-Hong, Xu Yong, Chen Xiao, Li Hui-Jie
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.
CAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China.
Neuroscience. 2020 Jun 1;436:74-81. doi: 10.1016/j.neuroscience.2020.04.011. Epub 2020 Apr 15.
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.
轻度认知障碍（MCI）患者被视为患阿尔茨海默病（AD）的高危人群。载脂蛋白E（APOE）ε4等位基因是已明确的AD发病遗传风险因素。在本研究中，我们通过体素镜像同伦连接（VMHC），旨在探索MCI APOE-ε4携带者潜在的功能紊乱。对35例MCI APOE-ε4携带者（27例APOE-ε3ε4，8例APOE-ε4ε4）和42例MCI APOE-ε4非携带者（APOE-ε3ε3）进行静息态功能磁共振成像。采用VMHC研究MCI APOE-ε4携带者的功能连接改变。我们进一步研究了两组中改变区域的VMHC值与其他脑区之间基于种子点的功能连接。结果显示，与非携带者相比，MCI APOE-ε4携带者在额下回/岛叶以及额中回/额上回的VMHC增加。我们发现，MCI APOE-ε4携带者在种子区域（双侧额下回/岛叶和双侧额中回/额上回）与包括额叶、颞叶、顶叶和小脑区域在内的广泛脑区之间的功能连接增强。我们的研究结果为APOE基因型对神经退行性疾病表型的调节提供了神经影像学证据，并且可能对监测AD双重高危人群的疾病进展具有潜在重要意义。
