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Association between GAB2 haplotype and higher glucose metabolism in Alzheimer's disease-affected brain regions in cognitively normal APOEε4 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) ε4 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 APOEε4 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 APOEε4 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 APOEε4 carriers. It also supports the use of brain-imaging endophenotypes to help assess possible modifiers of AD risk.

journal_name

Neuroimage

journal_title

NeuroImage

authors

Liang WS,Chen K,Lee W,Sidhar K,Corneveaux JJ,Allen AN,Myers A,Villa S,Meechoovet B,Pruzin J,Bandy D,Fleisher AS,Langbaum JB,Huentelman MJ,Jensen K,Dunckley T,Caselli RJ,Kaib S,Reiman EM

doi

10.1016/j.neuroimage.2010.09.066

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

1896-902

issue

3

eissn

1053-8119

issn

1095-9572

pii

S1053-8119(10)01268-1

journal_volume

54

pub_type

杂志文章

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