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Deletion of abca7 increases cerebral amyloid-β deposition in the J20 mouse model of Alzheimer’s disease

Conference Paper


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.

Authors


  •   Li, Henry (external author)
  •   Kim, Woojin S. (external author)
  •   Ruberu, Kalani R.
  •   Chan, Sharon (external author)
  •   Elliott, Doug (external author)
  •   Low, Jac Kee. (external author)
  •   Cheng, David (external author)
  •   Karl, Tim (external author)
  •   Garner, Brett

Publication Date


  • 2013

Citation


  • 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.

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/310

Start Page


  • 125

End Page


  • 125

Place Of Publication


  • Australia

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.

Authors


  •   Li, Henry (external author)
  •   Kim, Woojin S. (external author)
  •   Ruberu, Kalani R.
  •   Chan, Sharon (external author)
  •   Elliott, Doug (external author)
  •   Low, Jac Kee. (external author)
  •   Cheng, David (external author)
  •   Karl, Tim (external author)
  •   Garner, Brett

Publication Date


  • 2013

Citation


  • 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.

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/310

Start Page


  • 125

End Page


  • 125

Place Of Publication


  • Australia