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An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer's disease pathology following closed head injury: evidence of pharmacogenomic interaction.

Publication ,  Journal Article
Wang, H; Durham, L; Dawson, H; Song, P; Warner, DS; Sullivan, PM; Vitek, MP; Laskowitz, DT
Published in: Neuroscience
February 23, 2007

Apolipoprotein E (apoE) modifies glial activation and the CNS inflammatory response in an isoform-specific manner. Peptides derived from the receptor-binding region of apoE have been demonstrated to maintain the functional activity of the intact protein, and to improve histological and functional deficits after closed head injury. In the current study, APOE2, APOE3, and APOE4 targeted replacement (TR) mice expressing the human apoE protein isoforms (apoE2, apoE3 and apoE4) were used in a clinically relevant model of closed head injury to assess the interaction between the humanized apoE background and the therapeutic apoE mimetic peptide, apoE(133-149). Treatment with the apoE-mimetic peptide reduced microglial activation and early inflammatory events in all of the targeted replacement animals and was associated with histological and functional improvement in the APOE2TR and APOE3TR animals. Similarly, brain beta amyloid protein (Abeta)(1-42) levels were increased as a function of head injury in all of the targeted replacement mice, while treatment with apoE peptide suppressed Abeta(1-42) levels in the APOE2TR and APOE3TR animals. These results suggest a pharmacogenomic interaction between the therapeutic effects of the apoE mimetic peptide and the human apoE protein isoforms. Furthermore, they suggest that administration of apoE-mimetic peptides may serve as a novel therapeutic strategy for the treatment of acute and chronic neurological disease.

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Published In

Neuroscience

DOI

ISSN

0306-4522

Publication Date

February 23, 2007

Volume

144

Issue

4

Start / End Page

1324 / 1333

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Plaque, Amyloid
  • Peptide Fragments
  • Neurology & Neurosurgery
  • Microglia
  • Mice, Transgenic
  • Mice
  • Humans
  • Head Injuries, Closed
  • Gliosis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, H., Durham, L., Dawson, H., Song, P., Warner, D. S., Sullivan, P. M., … Laskowitz, D. T. (2007). An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer's disease pathology following closed head injury: evidence of pharmacogenomic interaction. Neuroscience, 144(4), 1324–1333. https://doi.org/10.1016/j.neuroscience.2006.11.017
Wang, H., L. Durham, H. Dawson, P. Song, D. S. Warner, P. M. Sullivan, M. P. Vitek, and D. T. Laskowitz. “An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer's disease pathology following closed head injury: evidence of pharmacogenomic interaction.Neuroscience 144, no. 4 (February 23, 2007): 1324–33. https://doi.org/10.1016/j.neuroscience.2006.11.017.
Wang, H., et al. “An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer's disease pathology following closed head injury: evidence of pharmacogenomic interaction.Neuroscience, vol. 144, no. 4, Feb. 2007, pp. 1324–33. Pubmed, doi:10.1016/j.neuroscience.2006.11.017.
Wang H, Durham L, Dawson H, Song P, Warner DS, Sullivan PM, Vitek MP, Laskowitz DT. An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer's disease pathology following closed head injury: evidence of pharmacogenomic interaction. Neuroscience. 2007 Feb 23;144(4):1324–1333.
Journal cover image

Published In

Neuroscience

DOI

ISSN

0306-4522

Publication Date

February 23, 2007

Volume

144

Issue

4

Start / End Page

1324 / 1333

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Plaque, Amyloid
  • Peptide Fragments
  • Neurology & Neurosurgery
  • Microglia
  • Mice, Transgenic
  • Mice
  • Humans
  • Head Injuries, Closed
  • Gliosis