Genome-wide association studies (GWAS) have implicated a series of single nucleotide polymorphisms (SNPs) in Alzheimer's disease (AD) risk. Elucidating the function of these SNPs is critical to identify the underlying pathways and, potentially, novel therapeutic agents. SNPs within the gene ATP binding cassette A7 (ABCA7) reached significance in these studies, warranting investigation into their actions. Here, we analyzed ABCA7 expression in a set of human brain samples as a function of AD-associated SNPs and AD status. We report that the rs3764650T allele that decreases AD risk is associated with increased ABCA7 expression. However, ABCA7 expression is increased in AD individuals. We interpret our findings as suggesting a model wherein increased ABCA7 expression reduces AD risk and that the increased ABCA7 observed in AD reflects an inadequate compensatory change.
Keywords: ABCA7; AD; ATP binding cassette A7; Alzheimer's; Alzheimer's disease; Aβ; EIF4H; GWAS; Microglia; Phagocytosis; RPL32; SNP; amyloid-beta; eukaryotic translation initiation factor 4H; genome-wide association studies; qPCR; quantitative polymerase chain reaction; ribosomal protein L32; single nucleotide polymorphism.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.