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Genetic influence of apolipoprotein E4 genotype on hippocampal morphometry: An N = 725 surface-based Alzheimer's disease neuroimaging initiative study

Authors

  • Jie Shi,

    1. School of Computing, Informatics, and Decision Systems Engineering, Arizona State University, Tempe, Arizona
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  • Natasha Leporé,

    1. Department of Radiology, Children's Hospital Los Angeles, Los Angeles, California
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  • Boris A. Gutman,

    1. Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, California
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  • Paul M. Thompson,

    1. Department of Neurology, Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, California
    2. Department of Psychiatry and Biobehavioral Sciences, Semel Institute, UCLA School of Medicine, Los Angeles, California
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  • Leslie C. Baxter,

    1. Human Brain Imaging Laboratory, Barrow Neurological Institute, Phoenix, Arizona
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  • Richard J. Caselli,

    1. Department of Neurology, Mayo Clinic Arizona, Scottsdale, Arizona
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  • Yalin Wang,

    Corresponding author
    1. School of Computing, Informatics, and Decision Systems Engineering, Arizona State University, Tempe, Arizona
    • Correspondence to: Dr. Yalin Wang, School of Computing, Informatics, and Decision Systems Engineering, Arizona State University, P.O. Box 878809, Tempe, Arizona 85287. E-mail: ylwang@asu.edu

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  • for the Alzheimer's Disease Neuroimaging Initiative

    1. School of Computing, Informatics, and Decision Systems Engineering, Arizona State University, Tempe, Arizona
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  • Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.ucla.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

  • Data collection and sharing for this project was funded by the Alzheimer'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 is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. 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's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514.

Abstract

The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer's disease (AD). Hippocampal volumes are generally smaller in AD patients carrying the e4 allele compared to e4 noncarriers. Here we examined the effect of APOE e4 on hippocampal morphometry in a large imaging database—the Alzheimer's Disease Neuroimaging Initiative (ADNI). We automatically segmented and constructed hippocampal surfaces from the baseline MR images of 725 subjects with known APOE genotype information including 167 with AD, 354 with mild cognitive impairment (MCI), and 204 normal controls. High-order correspondences between hippocampal surfaces were enforced across subjects with a novel inverse consistent surface fluid registration method. Multivariate statistics consisting of multivariate tensor-based morphometry (mTBM) and radial distance were computed for surface deformation analysis. Using Hotelling's T2 test, we found significant morphological deformation in APOE e4 carriers relative to noncarriers in the entire cohort as well as in the nondemented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes. Our findings are consistent with previous studies that showed e4 carriers exhibit accelerated hippocampal atrophy; we extend these findings to a novel measure of hippocampal morphometry. Hippocampal morphometry has significant potential as an imaging biomarker of early stage AD. Hum Brain Mapp 35:3903–3918, 2014. © 2014 Wiley Periodicals, Inc.

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