Influence ofAPOE Genotype on Whole-Brain Functional Networks in Cognitively Normal Elderly

This study aimed to investigate the influence of apolipoprotein E (APOE) epsilon 4 allele on whole-brain functional networks in cognitively normal (CN) elderly by applying graph theoretical analysis to brain glucose metabolism. Eighty-six CN elderly [28 APOE epsilon 4 carriers (epsilon 4+) and 58 non-carriers (epsilon 4-)] underwent clinical evaluation and resting [F-18] fluorodeoxyglucose positron emission tomography scan. Whole-brain functional networks were constructed from correlations of the 90 regions of interest using the automated anatomical labeling template, and analyzed using graph theoretical approaches. The overall small-world property seen in epsilon 4- was preserved in epsilon 4+. However, both local clustering and path length were lower in epsilon 4+ compared to epsilon 4-. In terms of the hubs of functional networks, epsilon 4+ showed decreased centrality of the right hippocampus but increased centrality of several brain regions associated with the default mode network compared to epsilon 4-. Our results indicate that genetic vulnerability to Alzheimer's disease may alter whole-brain functional networks even before clinical symptoms appear.This study was supported by a grant from the Seoul National University Hospital (Grant No. 2012-0568), a grant from the Korea Healthcare Technology R & D Project, Ministry of Health, Welfare & Family Affairs, Republic of Korea (Grant No. A092145), a grant from KIST Open Research Program (Grant No. 2013-1520), and a grant from Korea government (MEST) (Grant No. 2011-0028333). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript