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The APOE4 genotype alters the response of microglia and macrophages to 17beta-estradiol.

Publication ,  Journal Article
Brown, CM; Choi, E; Xu, Q; Vitek, MP; Colton, CA
Published in: Neurobiol Aging
December 2008

The apolipoprotein E4 (APOE4) gene is a well-known risk factor for Alzheimer's disease (AD) and other neurological disorders. Post-menopausal women with AD who express at least one APOE4 gene have more severe neuropathology and worsened cognitive scores than their non-expressing counterparts. Since 17beta-estradiol down-regulates inflammation as part of its neuroprotective role, we examined the effect of 17beta-estradiol on the response of microglia to immune activation as a function of APOE genotype. Our data show that the anti-inflammatory activity of 17beta-estradiol is significantly reduced in APOE4 targeted replacement mice compared to APOE3 mice. A significant interaction between APOE genotype and the response to 17beta-estradiol was observed for NO and cytokine production by immune activated microglia. The genotype specific effect was not restricted to brain macrophages since peritoneal macrophages from APOE4 ovariectomized mice also demonstrated a significant difference in 17beta-estradiol responsiveness. ERbeta protein levels in APOE4 microglia were higher than APOE3 microglia, suggesting a difference in post-translational protein regulation in the presence of the APOE4 gene. Overall, our data indicate that the APOE genotype may be a critical component in assessing the effectiveness of 17beta-estradiol's action and may impact the neuroprotective role of 17beta-estradiol and of hormone replacement therapy on brain function when the APOE4 gene is expressed.

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Published In

Neurobiol Aging

DOI

EISSN

1558-1497

Publication Date

December 2008

Volume

29

Issue

12

Start / End Page

1783 / 1794

Location

United States

Related Subject Headings

  • Ovariectomy
  • Neurology & Neurosurgery
  • Microglia
  • Mice, Transgenic
  • Mice
  • Macrophages
  • Female
  • Estradiol
  • Cells, Cultured
  • Apolipoprotein E4
 

Citation

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Brown, C. M., Choi, E., Xu, Q., Vitek, M. P., & Colton, C. A. (2008). The APOE4 genotype alters the response of microglia and macrophages to 17beta-estradiol. Neurobiol Aging, 29(12), 1783–1794. https://doi.org/10.1016/j.neurobiolaging.2007.04.018
Brown, Candice M., Emily Choi, Qing Xu, Michael P. Vitek, and Carol A. Colton. “The APOE4 genotype alters the response of microglia and macrophages to 17beta-estradiol.Neurobiol Aging 29, no. 12 (December 2008): 1783–94. https://doi.org/10.1016/j.neurobiolaging.2007.04.018.
Brown CM, Choi E, Xu Q, Vitek MP, Colton CA. The APOE4 genotype alters the response of microglia and macrophages to 17beta-estradiol. Neurobiol Aging. 2008 Dec;29(12):1783–94.
Brown, Candice M., et al. “The APOE4 genotype alters the response of microglia and macrophages to 17beta-estradiol.Neurobiol Aging, vol. 29, no. 12, Dec. 2008, pp. 1783–94. Pubmed, doi:10.1016/j.neurobiolaging.2007.04.018.
Brown CM, Choi E, Xu Q, Vitek MP, Colton CA. The APOE4 genotype alters the response of microglia and macrophages to 17beta-estradiol. Neurobiol Aging. 2008 Dec;29(12):1783–1794.
Journal cover image

Published In

Neurobiol Aging

DOI

EISSN

1558-1497

Publication Date

December 2008

Volume

29

Issue

12

Start / End Page

1783 / 1794

Location

United States

Related Subject Headings

  • Ovariectomy
  • Neurology & Neurosurgery
  • Microglia
  • Mice, Transgenic
  • Mice
  • Macrophages
  • Female
  • Estradiol
  • Cells, Cultured
  • Apolipoprotein E4