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
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.
N1 - Funding Information:
We would like to dedicate this work to our colleague Christopher Heward who passed while this study was being completed. We thank Patti Aguilar, Sandra Yee-Benedetto, David Branch, Sandra Goodwin, Debbie Intorcia, Jennifer Keppler, Barbara Knight, Les Mullen, Anita Prouty, Stephanie Reeder, Desiree Van Egmond, Justin Venditti, and Denise Brown for their assistance. We also thank Bruce Henslin, the study coordinator, Dr. Rosa Rademakers for performing APOE testing, and Mrs. Xiaofen Liu and Dr. Napatkamon Ayutyanont from the Banner PET center. This study was supported by Kronos Science Laboratory (to EMR), the National Institute of Mental Health ( R01MH57899 to EMR), the National Institute on Aging ( R01AG031581 and P30AG19610 to EMR), the Arizona Alzheimer's Disease Center ( AG023193 to EMR), the National Institute of Neurological Disorders and Stroke ( R01 NS059873 to MJH), and the State of Arizona (to EMR, MJH, and RJC). We thank our research volunteers for their participation.
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
SN - 1053-8119
VL - 54
SP - 1896
EP - 1902
JO - NeuroImage
JF - NeuroImage
IS - 3
ER -