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Apolipoprotein D modulates amyloid pathology in APP/PS1 Alzheimer's disease mice

Journal Article


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Abstract


  • Apolipoprotein D (apoD) is expressed in the brain and levels are increased in affected brain regions in Alzheimer's disease (AD). The role that apoD may play in regulating AD pathology has not been addressed. Here, we crossed both apoD-null mice and Thy-1 human apoD transgenic mice with APP-PS1 amyloidogenic AD mice. Loss of apoD resulted in a nearly 2-fold increase in hippocampal amyloid plaque load, as assessed by immunohistochemical staining. Conversely, transgenic expression of neuronal apoD reduced hippocampal plaque load by approximately 35%. This latter finding was associated with a 60% decrease in amyloid β 1-40 peptide levels, and a 34% decrease in insoluble amyloid β 1-42 peptide. Assessment of β-site amyloid precursor protein cleaving enzyme-1 (BACE1) levels and proteolytic products of amyloid precursor protein and neuregulin-1 point toward a possible association of altered BACE1 activity in association with altered apoD levels. In conclusion, the current studies provide clear evidence that apoD regulates amyloid plaque pathology in a mouse model of AD.

Authors


  •   Li, Henry (external author)
  •   Ruberu, Kalani R.
  •   Sanz Munoz, Sonia (external author)
  •   Jenner, Andrew M. (external author)
  •   Spiro, Adena S. (external author)
  •   Zhao, Peter
  •   Rassart, Eric (external author)
  •   Sanchez, Diego (external author)
  •   Ganfornina, Maria D. (external author)
  •   Karl, Tim (external author)
  •   Garner, Brett

Publication Date


  • 2015

Citation


  • Li, H., Ruberu, K., Sanz Munoz, S., Jenner, A. M., Spiro, A., Zhao, H., Rassart, E., Sanchez, D., Ganfornina, M. D., Karl, T. & Garner, B. (2015). Apolipoprotein D modulates amyloid pathology in APP/PS1 Alzheimer's disease mice. Neurobiology of Aging, 36 (5), 1820-1833.

Scopus Eid


  • 2-s2.0-84928714878

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1537&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/520

Has Global Citation Frequency


Number Of Pages


  • 13

Start Page


  • 1820

End Page


  • 1833

Volume


  • 36

Issue


  • 5

Place Of Publication


  • United States

Abstract


  • Apolipoprotein D (apoD) is expressed in the brain and levels are increased in affected brain regions in Alzheimer's disease (AD). The role that apoD may play in regulating AD pathology has not been addressed. Here, we crossed both apoD-null mice and Thy-1 human apoD transgenic mice with APP-PS1 amyloidogenic AD mice. Loss of apoD resulted in a nearly 2-fold increase in hippocampal amyloid plaque load, as assessed by immunohistochemical staining. Conversely, transgenic expression of neuronal apoD reduced hippocampal plaque load by approximately 35%. This latter finding was associated with a 60% decrease in amyloid β 1-40 peptide levels, and a 34% decrease in insoluble amyloid β 1-42 peptide. Assessment of β-site amyloid precursor protein cleaving enzyme-1 (BACE1) levels and proteolytic products of amyloid precursor protein and neuregulin-1 point toward a possible association of altered BACE1 activity in association with altered apoD levels. In conclusion, the current studies provide clear evidence that apoD regulates amyloid plaque pathology in a mouse model of AD.

Authors


  •   Li, Henry (external author)
  •   Ruberu, Kalani R.
  •   Sanz Munoz, Sonia (external author)
  •   Jenner, Andrew M. (external author)
  •   Spiro, Adena S. (external author)
  •   Zhao, Peter
  •   Rassart, Eric (external author)
  •   Sanchez, Diego (external author)
  •   Ganfornina, Maria D. (external author)
  •   Karl, Tim (external author)
  •   Garner, Brett

Publication Date


  • 2015

Citation


  • Li, H., Ruberu, K., Sanz Munoz, S., Jenner, A. M., Spiro, A., Zhao, H., Rassart, E., Sanchez, D., Ganfornina, M. D., Karl, T. & Garner, B. (2015). Apolipoprotein D modulates amyloid pathology in APP/PS1 Alzheimer's disease mice. Neurobiology of Aging, 36 (5), 1820-1833.

Scopus Eid


  • 2-s2.0-84928714878

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1537&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/520

Has Global Citation Frequency


Number Of Pages


  • 13

Start Page


  • 1820

End Page


  • 1833

Volume


  • 36

Issue


  • 5

Place Of Publication


  • United States