ABCA7 is a member of the highly conserved superfamily of ATP-binding cassette (ABC) transporters. These multipass transmembrane proteins use energy from ATP hydrolysis to transfer molecules across membrane barriers. ABCA7 is abundantly expressed in white blood cells, in macrophages, and in microglia, where it is thought to play a role in phagocytosis. The ABCA7 gene started drawing attention in Alzheimer’s disease research when a genome-wide association study (GWAS) identified it as a risk factor for late-onset AD. Subsequent meta-analysis confirmed the association, and the gene ranks among the top 10 risk genes on AlzGene. The association is strongest for African-Americans, in whom one ABCA7 variant was found to nearly double the risk of AD, with an effect size approaching that of ApoE.
Despite the evidence linking ABCA7 to AD, the underlying mechanism of ABCA7’s role in AD pathogenesis remains unknown. ABCA7 could impact AD pathogenesis through a variety of mechanisms, including regulation of APP processing and clearance of Aβ through phagocytosis. Overall, the identification of ABCA7 as an AD risk factor further strengthens the importance of lipid homeostasis in the development of the disease.
- AD GWAS in African Americans Confirms, Reshuffles AlzGene List
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- The ABC(A1)'s of Human ApoE—More Evidence for Isoform Differences
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