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

Jie Shi, Natasha Leporé, Boris A. Gutman, Paul M. Thompson, Leslie C. Baxter, Richard John Caselli, Yalin Wang

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3903-3918
Number of pages16
JournalHuman Brain Mapping
Volume35
Issue number8
DOIs
StatePublished - 2014

Fingerprint

Apolipoprotein E4
Neuroimaging
Apolipoproteins E
Alzheimer Disease
Genotype
Alleles
Homozygote
Heterozygote
Atrophy
Hippocampus
Biomarkers
Databases

Keywords

  • Alzheimer's disease
  • APOE e4
  • Hippocampus
  • MRI
  • Multivariate tensor-based morphometry

ASJC Scopus subject areas

  • Clinical Neurology
  • Anatomy
  • Neurology
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

Genetic influence of apolipoprotein E4 genotype on hippocampal morphometry : An N = 725 surface-based Alzheimer's disease neuroimaging initiative study. / Shi, Jie; Leporé, Natasha; Gutman, Boris A.; Thompson, Paul M.; Baxter, Leslie C.; Caselli, Richard John; Wang, Yalin.

In: Human Brain Mapping, Vol. 35, No. 8, 2014, p. 3903-3918.

Research output: Contribution to journalArticle

Shi, Jie ; Leporé, Natasha ; Gutman, Boris A. ; Thompson, Paul M. ; Baxter, Leslie C. ; Caselli, Richard John ; Wang, Yalin. / Genetic influence of apolipoprotein E4 genotype on hippocampal morphometry : An N = 725 surface-based Alzheimer's disease neuroimaging initiative study. In: Human Brain Mapping. 2014 ; Vol. 35, No. 8. pp. 3903-3918.
@article{8dc716dc61c44de08c9d8b20b24e504c,
title = "Genetic influence of apolipoprotein E4 genotype on hippocampal morphometry: An N = 725 surface-based Alzheimer's disease neuroimaging initiative study",
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.",
keywords = "Alzheimer's disease, APOE e4, Hippocampus, MRI, Multivariate tensor-based morphometry",
author = "Jie Shi and Natasha Lepor{\'e} and Gutman, {Boris A.} and Thompson, {Paul M.} and Baxter, {Leslie C.} and Caselli, {Richard John} and Yalin Wang",
year = "2014",
doi = "10.1002/hbm.22447",
language = "English (US)",
volume = "35",
pages = "3903--3918",
journal = "Human Brain Mapping",
issn = "1065-9471",
publisher = "Wiley-Liss Inc.",
number = "8",

}

TY - JOUR

T1 - Genetic influence of apolipoprotein E4 genotype on hippocampal morphometry

T2 - An N = 725 surface-based Alzheimer's disease neuroimaging initiative study

AU - Shi, Jie

AU - Leporé, Natasha

AU - Gutman, Boris A.

AU - Thompson, Paul M.

AU - Baxter, Leslie C.

AU - Caselli, Richard John

AU - Wang, Yalin

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - APOE e4

KW - Hippocampus

KW - MRI

KW - Multivariate tensor-based morphometry

UR - http://www.scopus.com/inward/record.url?scp=84903942060&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903942060&partnerID=8YFLogxK

U2 - 10.1002/hbm.22447

DO - 10.1002/hbm.22447

M3 - Article

C2 - 24453132

AN - SCOPUS:84903942060

VL - 35

SP - 3903

EP - 3918

JO - Human Brain Mapping

JF - Human Brain Mapping

SN - 1065-9471

IS - 8

ER -