Apolipoprotein E ε4 modulates functional brain connectome in Alzheimer's disease. Issue 5 (24th January 2015)

• Record Type: Journal Article
• Authors: Wang, Jinhui; Wang, Xiao; He, Yi; Yu, Xin; Wang, Huali; He, Yong
• Is Part Of: Human brain mapping. Volume 36:Issue 5(2015:May)
• Page Start: 1828
• Page End: 1846
• Publication Date: 2015-01-24
• Subjects: Brain mapping -- Periodicals; 611.81
• DOI: 10.1002/hbm.22740
• Languages: English
• ISSNs: 1065-9471

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>The apolipoprotein E (<italic>APOE</italic>) ɛ4 allele is a well‐established genetic risk factor for Alzheimer's disease (AD). Recent research has demonstrated an <italic>APOE</italic> ɛ4‐mediated modulation of intrinsic functional brain networks in cognitively normal individuals. However, it remains largely unknown whether and how <italic>APOE</italic> ɛ4 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 <italic>APOE</italic> ɛ4 carriers and 26 matched noncarriers with AD at three levels: global whole‐brain, intermediate module, and regional node/connection. Neuropsychological analysis showed that the <italic>APOE</italic> ɛ4 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 <italic>APOE</italic> ɛ4 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 <italic>APOE</italic> genotype modulates large‐scale brain networks in AD and shed new light on the gene‐connectome interaction in this disease. <italic>Hum Brain Mapp 36:1828–1846, 2015</italic>. © <bold>2015 Wiley Periodicals, Inc</bold>.</p> </abstract>