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Human APOE isoform-dependent effects on brain beta-amyloid levels in PDAPP transgenic mice.

Publication ,  Journal Article
Bales, KR; Liu, F; Wu, S; Lin, S; Koger, D; DeLong, C; Hansen, JC; Sullivan, PM; Paul, SM
Published in: J Neurosci
May 27, 2009

To investigate the role of human apolipoprotein E (apoE) on Abeta deposition in vivo, we crossed PDAPP mice lacking mouse Apoe to targeted replacement mice expressing human apoE (PDAPP/TRE2, PDAPP/TRE3, or PDAPP/TRE4). We then measured the levels of apoE protein and Abeta peptides in plasma, CSF, and brain homogenates in these mice at different ages. We also quantified the amount of brain Abeta and amyloid burden in 18-month-old mice. In young PDAPP/TRE4 mice that were analyzed at an age before brain Abeta deposition, we observed a significant decrease in the levels of apoE in CSF and brain when compared with age-matched mice expressing either human E2 or E3. The brain levels of Abeta42 in PDAPP/TRE4 mice were substantially elevated even at this very early time point. In older PDAPP/TRE4 mice, the levels of insoluble apoE protein increased in parallel to the dramatic rise in brain Abeta burden, and the majority of apoE was associated with Abeta. In TRE4 only mice, we also observed a significant decrease in the level of apoE in brain homogenates. Since the relative level of apoE mRNA was equivalent in PDAPP/TRE and TRE only mice, it appears that post-translational mechanisms influence the levels of apoE protein in brain (E4 < E3 << E2), resulting in early and dramatic apoE isoform-dependent effects on brain Abeta levels (E4 >> E3 > E2) that increase with age. Therapeutic strategies aimed at increasing the soluble levels of apoE protein, regardless of isoform, may effectively prevent and (or) treat Alzheimer's disease.

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Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

May 27, 2009

Volume

29

Issue

21

Start / End Page

6771 / 6779

Location

United States

Related Subject Headings

  • Protein Isoforms
  • Peptide Fragments
  • Neurology & Neurosurgery
  • Mutation
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Humans
  • Brain
  • Apolipoproteins E
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bales, K. R., Liu, F., Wu, S., Lin, S., Koger, D., DeLong, C., … Paul, S. M. (2009). Human APOE isoform-dependent effects on brain beta-amyloid levels in PDAPP transgenic mice. J Neurosci, 29(21), 6771–6779. https://doi.org/10.1523/JNEUROSCI.0887-09.2009
Bales, Kelly R., Feng Liu, Su Wu, Suizhen Lin, Deanna Koger, Cynthia DeLong, Jeffrey C. Hansen, Patrick M. Sullivan, and Steven M. Paul. “Human APOE isoform-dependent effects on brain beta-amyloid levels in PDAPP transgenic mice.J Neurosci 29, no. 21 (May 27, 2009): 6771–79. https://doi.org/10.1523/JNEUROSCI.0887-09.2009.
Bales KR, Liu F, Wu S, Lin S, Koger D, DeLong C, et al. Human APOE isoform-dependent effects on brain beta-amyloid levels in PDAPP transgenic mice. J Neurosci. 2009 May 27;29(21):6771–9.
Bales, Kelly R., et al. “Human APOE isoform-dependent effects on brain beta-amyloid levels in PDAPP transgenic mice.J Neurosci, vol. 29, no. 21, May 2009, pp. 6771–79. Pubmed, doi:10.1523/JNEUROSCI.0887-09.2009.
Bales KR, Liu F, Wu S, Lin S, Koger D, DeLong C, Hansen JC, Sullivan PM, Paul SM. Human APOE isoform-dependent effects on brain beta-amyloid levels in PDAPP transgenic mice. J Neurosci. 2009 May 27;29(21):6771–6779.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

May 27, 2009

Volume

29

Issue

21

Start / End Page

6771 / 6779

Location

United States

Related Subject Headings

  • Protein Isoforms
  • Peptide Fragments
  • Neurology & Neurosurgery
  • Mutation
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Humans
  • Brain
  • Apolipoproteins E