APOE Genotype Effects on Intrinsic Brain Network Connectivity in Patients with Amnestic Mild Cognitive Impairment.
Whether and how the apolipoprotein E (APOE) ε4 genotype specifically modulates brain network connectivity in patients with amnestic mild cognitive impairment (aMCI) remain largely unknown. Here, we employed resting-state ('task-free') functional MRI and network centrality approaches to investigate local (degree centrality, DC) and global (eigenvector centrality, EC) functional integrity in the whole-brain connectome in 156 older adults, including 66 aMCI patients (27 ε4-carriers and 39 non-carriers) and 90 healthy controls (45 ε4-carriers and 45 non-carriers). We observed diagnosis-by-genotype interactions on DC in the left superior/middle frontal gyrus, right middle temporal gyrus and cerebellum, with higher values in the ε4-carriers than non-carriers in the aMCI group. We further observed diagnosis-by-genotype interactions on EC, with higher values in the right middle temporal gyrus but lower values in the medial parts of default-mode network in the ε4-carriers than non-carriers in the aMCI group. Notably, these genotype differences in DC or EC were absent in the control group. Finally, the network connectivity DC values were negatively correlated with cognitive performance in the aMCI ε4-carriers. Our findings suggest that the APOE genotype selectively modulates the functional integration of brain networks in patients with aMCI, thus providing important insight into the gene-connectome interaction in this disease.
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China.
Zan
Z
Wang
Department of Psychology, Sun Yat-sen University, Guangzhou, 510006, China.|State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China.
Zhengjia
Z
Dai
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China.
Hao
H
Shu
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China.
Xuhong
X
Liao
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China.
Chunxian
C
Yue
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China.
Duan
D
Liu
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Qihao
Q
Guo
State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China. yong.he@bnu.edu.cn.
Yong
Y
He
Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, 210009, China. janemengzhang@vip.163.com.
Zhijun
Z
Zhang
D000368:Aged; D000647:Amnesia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000503:physiopathology*; D060825:Cognitive Dysfunction / Q000150:complications / Q000235:genetics* / Q000503:physiopathology*; D063132:Connectome; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests
D053327:Apolipoprotein E4