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

Research output: Contribution to journalArticle

14 Scopus citations

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.

    Fingerprint

Keywords

  • Alzheimer's disease
  • Fluorodeoxyglucose positron emission tomography

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology

Cite this

Liang, W. S., Chen, K., Lee, W., Sidhar, K., Corneveaux, J. J., Allen, A. N., Myers, A. J., Villa, S., Meechoovet, B., Pruzin, J., Bandy, D., Fleisher, A. S., Langbaum, J. B. S., Huentelman, M. J., Jensen, K., Dunckley, T., Caselli, R. J., Kaib, S., & Reiman, E. M. (2011). Association between GAB2 haplotype and higher glucose metabolism in Alzheimer's disease-affected brain regions in cognitively normal APOE?4 carriers. NeuroImage, 54(3), 1896-1902. https://doi.org/10.1016/j.neuroimage.2010.09.066