Whether and how the apolipoprotein E (APOE) epsilon 4 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 epsilon 4-carriers and 39 non-carriers) and 90 healthy controls (45 epsilon 4-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 epsilon 4-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 epsilon 4-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 epsilon 4-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.
[1]Southeast Univ, Affiliated ZhongDa Hosp, Sch Med, Dept Neurol, Nanjing 210009, Jiangsu, Peoples R China.
[2]Sun Yat Sen Univ, Dept Psychol, Guangzhou 510006, Guangdong, Peoples R China.
[3]Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China.
[4]Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China.
[5]Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai 200040, Peoples R China.
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