Genetic influence of apolipoprotein E4 genotype on hippocampal morphometry: An <i>N</i> = 725 surface‐based Alzheimer's disease neuroimaging initiative study

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  • Jie Shi
    School of Computing, Informatics, and Decision Systems Engineering, Arizona State University Tempe Arizona
  • Natasha Leporé
    Department of Radiology Children's Hospital Los Angeles Los Angeles California
  • Boris A. Gutman
    Imaging Genetics Center Institute for Neuroimaging and Informatics University of Southern California Los Angeles California
  • Paul M. Thompson
    Department of Neurology Imaging Genetics Center Laboratory of Neuro Imaging UCLA School of Medicine Los Angeles California
  • Leslie C. Baxter
    Human Brain Imaging Laboratory, Barrow Neurological Institute Phoenix Arizona
  • Richard J. Caselli
    Department of Neurology Mayo Clinic Arizona Scottsdale Arizona
  • Yalin Wang
    School of Computing, Informatics, and Decision Systems Engineering, Arizona State University Tempe Arizona

書誌事項

公開日
2014-01-22
権利情報
  • http://onlinelibrary.wiley.com/termsAndConditions#vor
DOI
  • 10.1002/hbm.22447
公開者
Wiley

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説明

<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>T</jats:italic><jats:sup>2</jats:sup> 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. <jats:italic>Hum Brain Mapp 35:3903–3918, 2014</jats:italic>. © <jats:bold>2014 Wiley Periodicals, Inc</jats:bold>.</jats:p>

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