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Human apolipoprotein E4 worsens acute axonal pathology but not amyloid-β immunoreactivity after traumatic brain injury in 3xTG-AD mice.

Publication ,  Journal Article
Bennett, RE; Esparza, TJ; Lewis, HA; Kim, E; Mac Donald, CL; Sullivan, PM; Brody, DL
Published in: J Neuropathol Exp Neurol
May 2013

Apolipoprotein E4 (APOE4) genotype is a risk factor for poor outcome after traumatic brain injury (TBI), particularly in young patients, but the underlying mechanisms are not known. By analogy to effects of APOE4 on the risk of Alzheimer disease (AD), the APOE genotype may influence β-amyloid (Aβ) and tau deposition after TBI. To test this hypothesis, we crossed 3xTG-AD transgenic mice carrying 3 human familial AD mutations (PS1(M146V), tauP(301)L, and APP(SWE)) to human ApoE2-, ApoE3-, and ApoE4-targeted replacement mice. Six- to 8-month-old 3xTG-ApoE mice were assayed by quantitative immunohistochemistry for amyloid precursor protein (APP), Aβ(1-40) (Aβ40), Aβ(1-42) (Aβ42), total human tau, and phospho-serine 199 (pS199) tau at 24 hours after moderate controlled cortical impact. There were increased numbers of APP-immunoreactive axonal varicosities in 3xTG-ApoE4 mice versus the other genotypes. This finding was repeated in a separate cohort of ApoE4-targeted replacement mice without human transgenes compared with ApoE3 and ApoE2 mice. There were no differences between genotypes in the extent of intra-axonal Aβ40 and Aβ42; none of the mice had extracellular Aβ deposition. Regardless of injury status, 3xTG-ApoE4 mice had more total human tau accumulation in both somatodendritic and intra-axonal compartments than other genotypes. These results suggest that the APOE4 genotype may have a primary effect on the severity of axonal injury in acute TBI.

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Published In

J Neuropathol Exp Neurol

DOI

EISSN

1554-6578

Publication Date

May 2013

Volume

72

Issue

5

Start / End Page

396 / 403

Location

England

Related Subject Headings

  • Random Allocation
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice
  • Male
  • Immunohistochemistry
  • Humans
  • Female
  • Brain Injuries
  • Axons
 

Citation

APA
Chicago
ICMJE
MLA
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Bennett, R. E., Esparza, T. J., Lewis, H. A., Kim, E., Mac Donald, C. L., Sullivan, P. M., & Brody, D. L. (2013). Human apolipoprotein E4 worsens acute axonal pathology but not amyloid-β immunoreactivity after traumatic brain injury in 3xTG-AD mice. J Neuropathol Exp Neurol, 72(5), 396–403. https://doi.org/10.1097/NEN.0b013e31828e24ab
Bennett, Rachel E., Thomas J. Esparza, Hal A. Lewis, Eddie Kim, Christine L. Mac Donald, Patrick M. Sullivan, and David L. Brody. “Human apolipoprotein E4 worsens acute axonal pathology but not amyloid-β immunoreactivity after traumatic brain injury in 3xTG-AD mice.J Neuropathol Exp Neurol 72, no. 5 (May 2013): 396–403. https://doi.org/10.1097/NEN.0b013e31828e24ab.
Bennett RE, Esparza TJ, Lewis HA, Kim E, Mac Donald CL, Sullivan PM, et al. Human apolipoprotein E4 worsens acute axonal pathology but not amyloid-β immunoreactivity after traumatic brain injury in 3xTG-AD mice. J Neuropathol Exp Neurol. 2013 May;72(5):396–403.
Bennett, Rachel E., et al. “Human apolipoprotein E4 worsens acute axonal pathology but not amyloid-β immunoreactivity after traumatic brain injury in 3xTG-AD mice.J Neuropathol Exp Neurol, vol. 72, no. 5, May 2013, pp. 396–403. Pubmed, doi:10.1097/NEN.0b013e31828e24ab.
Bennett RE, Esparza TJ, Lewis HA, Kim E, Mac Donald CL, Sullivan PM, Brody DL. Human apolipoprotein E4 worsens acute axonal pathology but not amyloid-β immunoreactivity after traumatic brain injury in 3xTG-AD mice. J Neuropathol Exp Neurol. 2013 May;72(5):396–403.
Journal cover image

Published In

J Neuropathol Exp Neurol

DOI

EISSN

1554-6578

Publication Date

May 2013

Volume

72

Issue

5

Start / End Page

396 / 403

Location

England

Related Subject Headings

  • Random Allocation
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice
  • Male
  • Immunohistochemistry
  • Humans
  • Female
  • Brain Injuries
  • Axons