| Title | Apolipoprotein E epsilon 4 Modulates Functional Brain Connectome in Alzheimer's Disease |
| Authors | Wang, Jinhui Wang, Xiao He, Yi Yu, Xin Wang, Huali He, Yong |
| Affiliation | Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China. Hangzhou Normal Univ, Ctr Cognit & Brain Disorders, Hangzhou, Zhejiang, Peoples R China. Zhejiang Key Lab Res Assessment Cognit Impairment, Hangzhou, Zhejiang, Peoples R China. Peking Univ, Inst Mental Hlth, Dementia Care & Res Ctr, Beijing 100871, Peoples R China. Peking Univ, Key Lab Mental Hlth, Minist Hlth, Beijing 100871, Peoples R China. Beijing Normal Univ, Ctr Collaborat & Innovat Brain & Learning Sci, Beijing 100875, Peoples R China. Peking Univ, Inst Mental Hlth, Beijing, Peoples R China. |
| Keywords | connectomics graph theory functional connectivity module default mode resting-state fMRI SMALL-WORLD NETWORKS RESTING-STATE APOE GENOTYPE GENETIC RISK CORTICAL NETWORKS CONNECTIVITY MRI DEFAULT NETWORK WORKING-MEMORY AMYLOID BURDEN OLDER PERSONS |
| Issue Date | 2015 |
| Publisher | HUMAN BRAIN MAPPING |
| Citation | HUMAN BRAIN MAPPING.2015,36,(5),1828-1846. |
| Abstract | The apolipoprotein E (APOE) 4 allele is a well-established genetic risk factor for Alzheimer's disease (AD). Recent research has demonstrated an APOE 4-mediated modulation of intrinsic functional brain networks in cognitively normal individuals. However, it remains largely unknown whether and how APOE 4 affects the brain's functional network architecture in patients with AD. Using resting-state functional MRI and graph-theory approaches, we systematically investigated the topological organization of whole-brain functional networks in 16 APOE 4 carriers and 26 matched noncarriers with AD at three levels: global whole-brain, intermediate module, and regional node/connection. Neuropsychological analysis showed that the APOE 4 carriers performed worse on delayed memory but better on a late item generation of a verbal fluency task (associated with executive function) than noncarriers. Whole-brain graph analyses revealed that APOE 4 significantly disrupted whole-brain topological organization as characterized by (i) reduced parallel information transformation efficiency; (ii) decreased intramodular connectivity within the posterior default mode network (pDMN) and intermodular connectivity of the pDMN and executive control network (ECN) with other neuroanatomical systems; and (iii) impaired functional hubs and their rich-club connectivities that primarily involve the pDMN, ECN, and sensorimotor systems. Further simulation analysis indicated that these altered connectivity profiles of the pDMN and ECN largely accounted for the abnormal global network topology. Finally, the changes in network topology exhibited significant correlations with the patients' cognitive performances. Together, our findings suggest that the APOE genotype modulates large-scale brain networks in AD and shed new light on the gene-connectome interaction in this disease. Hum Brain Mapp 36:1828-1846, 2015. (c) 2015 Wiley Periodicals, Inc. |
| URI | http://hdl.handle.net/20.500.11897/420392 |
| ISSN | 1065-9471 |
| DOI | 10.1002/hbm.22740 |
| Indexed | SCI(E) |
| Appears in Collections: | 第六医院 |
