@article{26356d5e83b04b878fd75fdc4d60fa79,
title = "Default Mode Network Analysis of APOE Genotype in Cognitively Unimpaired Subjects Based on Persistent Homology",
abstract = "Current researches on default mode network (DMN) in normal elderly have mainly focused on finding some dysfunctional areas with decreased or increased connectivity. The global network dynamics of apolipoprotein E (APOE) e4 allele group is rarely studied. In our previous brain network study, we have demonstrated the advantage of persistent homology. It can distinguish robust and noisy topological features over multiscale nested networks, and the derived properties are more stable. In this study, for the first time we applied persistent homology to analyze APOE-related effects on whole-brain functional network. In our experiments, the risk allele group exhibited lower network radius and modularity in whole brain DMN based on graph theory, suggesting the abnormal organization structure. Moreover, two suggested measures from persistent homology detected significant differences between groups within the left hemisphere and in the whole brain in two datasets. They were more statistically sensitive to APOE genotypic differences than standard graph-based measures. In summary, we provide evidence that the e4 genotype leads to distinct DMN functional alterations in the early phases of Alzheimer{\textquoteright}s disease using persistent homology approach. Our study offers a novel insight to explore potential biomarkers in healthy elderly populations carrying APOE e4 allele.",
keywords = "APOE, Alzheimer{\textquoteright}s disease, graph theory, network measure, persistent homology, resting state functional magnetic resonance imaging",
author = "{for the Alzheimer's Disease Neuroimaging Initiative} and Liqun Kuang and Jiaying Jia and Deyu Zhao and Fengguang Xiong and Xie Han and Yalin Wang",
note = "Funding Information: Data collection and sharing for this project was funded by the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI was funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer{\textquoteright}s Association; Alzheimer{\textquoteright}s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer{\textquoteright}s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuroimaging at the University of Southern California. Funding. This research was funded by the National Key Research and Development Program of China (2018YFB2101504 to LK, FX, and XH), the Shanxi Provincial Key Research and Development Project (201803D121081 and 201903D121147 to LK, FX, and XH), the Natural Science Foundation of Shanxi Province of China (201901D111150 to LK, FX, and XH), the Graduate Science and Technology Project at North University of China (20191638 to JJ), the National Institute on Aging (R21AG043760, R21AG049216, and RF1AG051710 to YW), the National Institute of Biomedical Imaging and Bioengineering (R01EB025032 to YW), the National Heart, Lung, and Blood Institute (R01HL128818 to YW), and the National Science Foundation (DMS-1413417 and IIS-1421165 to YW). Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Kuang, Jia, Zhao, Xiong, Han and Wang for the Alzheimer{\textquoteright}s Disease Neuroimaging Initiative.",
year = "2020",
month = jun,
day = "30",
doi = "10.3389/fnagi.2020.00188",
language = "English (US)",
volume = "12",
journal = "Frontiers in Aging Neuroscience",
issn = "1663-4365",
publisher = "Frontiers Research Foundation",
}