Introduction of ABCA7
ABCA7 encoded by ABCA7 gene is a member of the superfamily of ATP-binding cassette (ABC) transporters which transport various molecules across extra- and intracellular membranes. There are seven subfamilies in ABC superfamily named as ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White, respectively. ABCA7 protein belongs to ABC1 subfamily. It is highly expressed in peripheral leukocytes, thymus, spleen, and bone marrow.
|Basic Information of ABCA7|
|Protein Name||ATP-binding cassette sub-family A member 7|
|Aliases||AD9, ABCX, ABCA-SSN|
|Organism||Homo sapiens (Human)|
Function of ABCA7 Membrane Protein
ABCA7 is an integrated transport protein that transports lipid molecules across extra- and intracellular membranes involved in the regulation of lipid homeostasis within defined microenvironments. In female mice, ABCA7 knockout can significantly reduce visceral fat and serum cholesterol concentrations. It has been reported that ABCA7 plays an essential role in the progression of Alzheimer’s disease (AD). The highest levels of ABCA7 are observed in the hippocampus that is one of the earliest affected regions in the brains of patients with AD, and in microglia cells responsible for cerebral inflammatory responses. Moreover, ABCA7 may be involved in the microglial amyloid-β (Aβ) clearance pathway that is a protective factor for AD. The deficiency of ABCA7 leads to the accumulation of Aβ thereby triggering the pathogenic cascade of AD. Several GWASs (Genome Wide Association Study) have revealed that variants in ABCA7 genes, especially loss-of-function variants, are associated with significant risk for AD. In addition, ABCA7 is also found in a variety of immune cells suggesting a role in immune response. However, the role of ABCA7 in the immune response is unknown.
Fig.1 Possible pathogenic pathways mediated by ABCA7 in AD. (Aikawa, 2018)
Application of ABCA7 Membrane Protein in Literature
The meta-analysis study shows that the loss-of-function variants in ABCA7 are significantly linked to the susceptibility to Alzheimer's Disease.
The meta-analysis study shows that ABCA7 (rs3764650), CR1 (rs6656401), and BIN1 (rs744373) are the risk factors of late-onset Alzheimer's disease (LOAD), while MS4A6A (rs610932) and CLU (rs11136000) are the protective factors.
The authors identify 2 rare variants in ABCA7 (rs143718918 and rs538591288) are associated with the development of Alzheimer Disease (AD) in 2 German families. These suggest ABCA7 is one of the most relevant genes of AD risk.
The study shows that the dysfunctions of ABCA7 are associated with the AD-related of Alzheimer's disease involved in multiple pathways such as microglial Aβ clearance pathway.
The authors identify the association of ABCA7 rs3764650 polymorphism with the risk of Alzheimer's disease (AD) using a meta-analysis.
ABCA7 Preparation Options
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