APOE Genotype Effects on Intrinsic Brain Network Connectivity in Patients with Amnestic Mild Cognitive Impairment

Zan Wang,Zhengjia Dai,Zhijun Zhang,Hao Shu,Yong He,Duan Liu,Qihao Guo,Chunxian Yue,Xuhong Liao

doi:10.1038/s41598-017-00432-0

Abstract

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.

Highlights

Two-way analysis of covariance (ANCOVA) analyses revealed the main effects of diagnosis and apolipoprotein E (APOE) genotype and the diagnosis-by-genotype interactions on neurocognitive measures
We observed a significant interaction between diagnosis and APOE genotype only on visuospatial function, with ε4 carriers showing worse performance than non-carriers in the amnestic mild cognitive impairment (aMCI) group but no genotype difference in the healthy controls (HCs) group
We found that the degree centrality (DC) values in the left SFG/MFG, right middle temporal gyrus (MTG)/HIP and right PLC were negatively correlated with the cognitive performance in the aMCI ε4 carriers (Fig. 4A–C, red circles)

Summary

Introduction

Numerous functional magnetic resonance imaging (fMRI)/magnetoencephalography (MEG)/electroencephagraphy (EEG) studies reported the alterations of the brain’s structural and functional connectivity in either patients with aMCI17–20 or healthy APOE ε4 carriers[21,22,23,24,25], suggesting the association of the presence of aMCI or APOE ε4 status with the alterations of neuronal circuits. In the present study, we will use the resting-state (‘task-free’) functional magnetic resonance imaging data to construct the functional brain network and further investigate how the APOE genotype modulates brain network connectivity in patients with aMCI. We employed resting-state functional magnetic resonance imaging (R-fMRI) to investigate the functional connectivity patterns of the whole-brain networks in 156 individuals including 66 aMCI patients (27 ε4 carriers and 39 non-carriers) and 90 healthy controls (45 ε4 carriers and 45 non-carriers). We hypothesize that the APOE ε4 is linked to a specific pattern of intrinsic functional disintegration of the brain networks in patients with aMCI

Methods

Results

Conclusion