Deletion of ABCA7 increases cerebral amyloid-β deposition in the J20 mouse model of Alzheimer's disease
RIS ID
80289
Abstract
ATP-binding cassette transporter A7 (ABCA7) is expressed in the brain and has been detected in macrophages, microglia, and neurons. ABCA7 promotes efflux of lipids from cells to apolipoproteins. ABCA7 can also regulate phagocytosis and modulate processing of amyloid precursor protein (APP) to generate the Alzheimer’s disease (AD) amyloid-β (Aβ) peptide. Genome-wide association studies indicate ABCA7 SNPs confer increased risk for late-onset AD; however, the role that ABCA7 plays in the brain in the AD context is unknown. In the present study we crossed ABCA7 deficient (A7-/-) mice with J20 amyloidogenic mice to address this issue. We show that ABCA7 loss doubled insoluble Aβ levels and thioflavine-S positive plaques in the brain. This was not related to changes in APP processing (assessed by analysis of full-length APP and the APP β C-terminal fragment). Apolipoprotein E (apoE) regulates cerebral Aβ homeostasis and plaque load, however, apoE concentration was not altered by ABCA7 loss. Spatial reference memory was significantly impaired in both J20 and J20/A7-/- mice compared to wild type mice; however, there were no cognitive differences comparing J20 and J20/A7-/- mice. There were also no major differences detected in hippocampal or plaque-associated microglial/macrophage markers when J20 and J20/A7-/- mice were compared, whereas the capacity for macrophages derived from A7-/- mice to take up oligomeric Aβ was reduced by 51% compared to wild type mice. Our studies suggest ABCA7 plays a role in the regulation of Aβ homeostasis in the brain and that this may be related to altered phagocyte function.
Publication Details
Li, H., Kim, W. S., Ruberu, K., Chan, S., Elliott, D., Low, J. K., Cheng, D., Karl, T. & Garner, B. (2013). Deletion of ABCA7 increases cerebral amyloid-β deposition in the J20 mouse model of Alzheimer's disease. 33rd Meeting of the Australian Neuroscience Society: Program, Abstracts & List of Registrants (pp. 125-125). Australia: ANS.