Association between GAB2 haplotype and higher glucose metabolism in Alzheimer's disease-affected brain regions in cognitively normal APOE?4 carriers

Winnie S. Liang, Kewei Chen, Wendy Lee, Kunal Sidhar, Jason J. Corneveaux, April N. Allen, Amanda J Myers, Stephen Villa, Bessie Meechoovet, Jeremy Pruzin, Daniel Bandy, Adam S. Fleisher, Jessica B S Langbaum, Matthew J. Huentelman, Kendall Jensen, Travis Dunckley, Richard J. Caselli, Susan Kaib, Eric M. Reiman

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

In a genome-wide association study (GWAS) of late-onset Alzheimer's disease (AD), we found an association between common haplotypes of the GAB2 gene and AD risk in carriers of the apolipoprotein E (APOE) ?4 allele, the major late-onset AD susceptibility gene. We previously proposed the use of fluorodeoxyglucose positron emission tomography (FDG-PET) measurements as a quantitative pre-symptomatic endophenotype, more closely related to disease risk than the clinical syndrome itself, to help evaluate putative genetic and non-genetic modifiers of AD risk. In this study, we examined the relationship between the presence or absence of the relatively protective GAB2 haplotype and PET measurements of regional-to-whole brain FDG uptake in several AD-affected brain regions in 158 cognitively normal late-middle-aged APOE?4 homozygotes, heterozygotes, and non-carriers. GAB2 haplotypes were characterized using Affymetrix Genome-Wide Human SNP 6.0 Array data from each of these subjects. As predicted, the possibly protective GAB2 haplotype was associated with higher regional-to-whole brain FDG uptake in AD-affected brain regions in APOE?4 carriers. While additional studies are needed, this study supports the association between the possibly protective GAB2 haplotype and the risk of late-onset AD in APOE?4 carriers. It also supports the use of brain-imaging endophenotypes to help assess possible modifiers of AD risk.

Original languageEnglish
Pages (from-to)1896-1902
Number of pages7
JournalNeuroImage
Volume54
Issue number3
DOIs
StatePublished - Feb 1 2011
Externally publishedYes

Fingerprint

Apolipoproteins E
Haplotypes
Alzheimer Disease
Glucose
Brain
Endophenotypes
Genome-Wide Association Study
Disease Susceptibility
Homozygote
Human Genome
Heterozygote
Neuroimaging
Positron-Emission Tomography
Genes
Single Nucleotide Polymorphism
Alleles

Keywords

  • Alzheimer's disease
  • Fluorodeoxyglucose positron emission tomography

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology

Cite this

Association between GAB2 haplotype and higher glucose metabolism in Alzheimer's disease-affected brain regions in cognitively normal APOE?4 carriers. / Liang, Winnie S.; Chen, Kewei; Lee, Wendy; Sidhar, Kunal; Corneveaux, Jason J.; Allen, April N.; Myers, Amanda J; Villa, Stephen; Meechoovet, Bessie; Pruzin, Jeremy; Bandy, Daniel; Fleisher, Adam S.; Langbaum, Jessica B S; Huentelman, Matthew J.; Jensen, Kendall; Dunckley, Travis; Caselli, Richard J.; Kaib, Susan; Reiman, Eric M.

In: NeuroImage, Vol. 54, No. 3, 01.02.2011, p. 1896-1902.

Research output: Contribution to journalArticle

Liang, WS, Chen, K, Lee, W, Sidhar, K, Corneveaux, JJ, Allen, AN, Myers, AJ, Villa, S, Meechoovet, B, Pruzin, J, Bandy, D, Fleisher, AS, Langbaum, JBS, Huentelman, MJ, Jensen, K, Dunckley, T, Caselli, RJ, Kaib, S & Reiman, EM 2011, 'Association between GAB2 haplotype and higher glucose metabolism in Alzheimer's disease-affected brain regions in cognitively normal APOE?4 carriers', NeuroImage, vol. 54, no. 3, pp. 1896-1902. https://doi.org/10.1016/j.neuroimage.2010.09.066
Liang, Winnie S. ; Chen, Kewei ; Lee, Wendy ; Sidhar, Kunal ; Corneveaux, Jason J. ; Allen, April N. ; Myers, Amanda J ; Villa, Stephen ; Meechoovet, Bessie ; Pruzin, Jeremy ; Bandy, Daniel ; Fleisher, Adam S. ; Langbaum, Jessica B S ; Huentelman, Matthew J. ; Jensen, Kendall ; Dunckley, Travis ; Caselli, Richard J. ; Kaib, Susan ; Reiman, Eric M. / Association between GAB2 haplotype and higher glucose metabolism in Alzheimer's disease-affected brain regions in cognitively normal APOE?4 carriers. In: NeuroImage. 2011 ; Vol. 54, No. 3. pp. 1896-1902.
@article{a84765d69f674f39b145c6bcd3f9a858,
title = "Association between GAB2 haplotype and higher glucose metabolism in Alzheimer's disease-affected brain regions in cognitively normal APOE?4 carriers",
abstract = "In a genome-wide association study (GWAS) of late-onset Alzheimer's disease (AD), we found an association between common haplotypes of the GAB2 gene and AD risk in carriers of the apolipoprotein E (APOE) ?4 allele, the major late-onset AD susceptibility gene. We previously proposed the use of fluorodeoxyglucose positron emission tomography (FDG-PET) measurements as a quantitative pre-symptomatic endophenotype, more closely related to disease risk than the clinical syndrome itself, to help evaluate putative genetic and non-genetic modifiers of AD risk. In this study, we examined the relationship between the presence or absence of the relatively protective GAB2 haplotype and PET measurements of regional-to-whole brain FDG uptake in several AD-affected brain regions in 158 cognitively normal late-middle-aged APOE?4 homozygotes, heterozygotes, and non-carriers. GAB2 haplotypes were characterized using Affymetrix Genome-Wide Human SNP 6.0 Array data from each of these subjects. As predicted, the possibly protective GAB2 haplotype was associated with higher regional-to-whole brain FDG uptake in AD-affected brain regions in APOE?4 carriers. While additional studies are needed, this study supports the association between the possibly protective GAB2 haplotype and the risk of late-onset AD in APOE?4 carriers. It also supports the use of brain-imaging endophenotypes to help assess possible modifiers of AD risk.",
keywords = "Alzheimer's disease, Fluorodeoxyglucose positron emission tomography",
author = "Liang, {Winnie S.} and Kewei Chen and Wendy Lee and Kunal Sidhar and Corneveaux, {Jason J.} and Allen, {April N.} and Myers, {Amanda J} and Stephen Villa and Bessie Meechoovet and Jeremy Pruzin and Daniel Bandy and Fleisher, {Adam S.} and Langbaum, {Jessica B S} and Huentelman, {Matthew J.} and Kendall Jensen and Travis Dunckley and Caselli, {Richard J.} and Susan Kaib and Reiman, {Eric M.}",
year = "2011",
month = "2",
day = "1",
doi = "10.1016/j.neuroimage.2010.09.066",
language = "English",
volume = "54",
pages = "1896--1902",
journal = "NeuroImage",
issn = "1053-8119",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Association between GAB2 haplotype and higher glucose metabolism in Alzheimer's disease-affected brain regions in cognitively normal APOE?4 carriers

AU - Liang, Winnie S.

AU - Chen, Kewei

AU - Lee, Wendy

AU - Sidhar, Kunal

AU - Corneveaux, Jason J.

AU - Allen, April N.

AU - Myers, Amanda J

AU - Villa, Stephen

AU - Meechoovet, Bessie

AU - Pruzin, Jeremy

AU - Bandy, Daniel

AU - Fleisher, Adam S.

AU - Langbaum, Jessica B S

AU - Huentelman, Matthew J.

AU - Jensen, Kendall

AU - Dunckley, Travis

AU - Caselli, Richard J.

AU - Kaib, Susan

AU - Reiman, Eric M.

PY - 2011/2/1

Y1 - 2011/2/1

N2 - In a genome-wide association study (GWAS) of late-onset Alzheimer's disease (AD), we found an association between common haplotypes of the GAB2 gene and AD risk in carriers of the apolipoprotein E (APOE) ?4 allele, the major late-onset AD susceptibility gene. We previously proposed the use of fluorodeoxyglucose positron emission tomography (FDG-PET) measurements as a quantitative pre-symptomatic endophenotype, more closely related to disease risk than the clinical syndrome itself, to help evaluate putative genetic and non-genetic modifiers of AD risk. In this study, we examined the relationship between the presence or absence of the relatively protective GAB2 haplotype and PET measurements of regional-to-whole brain FDG uptake in several AD-affected brain regions in 158 cognitively normal late-middle-aged APOE?4 homozygotes, heterozygotes, and non-carriers. GAB2 haplotypes were characterized using Affymetrix Genome-Wide Human SNP 6.0 Array data from each of these subjects. As predicted, the possibly protective GAB2 haplotype was associated with higher regional-to-whole brain FDG uptake in AD-affected brain regions in APOE?4 carriers. While additional studies are needed, this study supports the association between the possibly protective GAB2 haplotype and the risk of late-onset AD in APOE?4 carriers. It also supports the use of brain-imaging endophenotypes to help assess possible modifiers of AD risk.

AB - In a genome-wide association study (GWAS) of late-onset Alzheimer's disease (AD), we found an association between common haplotypes of the GAB2 gene and AD risk in carriers of the apolipoprotein E (APOE) ?4 allele, the major late-onset AD susceptibility gene. We previously proposed the use of fluorodeoxyglucose positron emission tomography (FDG-PET) measurements as a quantitative pre-symptomatic endophenotype, more closely related to disease risk than the clinical syndrome itself, to help evaluate putative genetic and non-genetic modifiers of AD risk. In this study, we examined the relationship between the presence or absence of the relatively protective GAB2 haplotype and PET measurements of regional-to-whole brain FDG uptake in several AD-affected brain regions in 158 cognitively normal late-middle-aged APOE?4 homozygotes, heterozygotes, and non-carriers. GAB2 haplotypes were characterized using Affymetrix Genome-Wide Human SNP 6.0 Array data from each of these subjects. As predicted, the possibly protective GAB2 haplotype was associated with higher regional-to-whole brain FDG uptake in AD-affected brain regions in APOE?4 carriers. While additional studies are needed, this study supports the association between the possibly protective GAB2 haplotype and the risk of late-onset AD in APOE?4 carriers. It also supports the use of brain-imaging endophenotypes to help assess possible modifiers of AD risk.

KW - Alzheimer's disease

KW - Fluorodeoxyglucose positron emission tomography

UR - http://www.scopus.com/inward/record.url?scp=78650225602&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650225602&partnerID=8YFLogxK

U2 - 10.1016/j.neuroimage.2010.09.066

DO - 10.1016/j.neuroimage.2010.09.066

M3 - Article

C2 - 20888920

AN - SCOPUS:78650225602

VL - 54

SP - 1896

EP - 1902

JO - NeuroImage

JF - NeuroImage

SN - 1053-8119

IS - 3

ER -