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ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42.

Publication ,  Journal Article
Trommer, BL; Shah, C; Yun, SH; Gamkrelidze, G; Pasternak, ES; Stine, WB; Manelli, A; Sullivan, P; Pasternak, JF; LaDu, MJ
Published in: Neurobiol Dis
February 2005

Amyloid-beta1-42 (Abeta1-42) is crucial to Alzheimer disease (AD) pathogenesis but the conformation of the toxic Abeta species remains uncertain. AD risk is increased by apolipoprotein E4 (apoE4) and decreased by apoE2 compared with the apoE3 isoform, but whether inheritance of apoE4 represents a gain of negative or a loss of protective function is also unresolved. Using hippocampal slices from apoE knockout (apoE-KO) and human apoE2, E3, and E4 targeted replacement (apoE-TR) mice, we found that oligomeric Abeta1-42 inhibited long-term potentiation (LTP) with a hierarchy of susceptibility mirroring clinical AD risk (apoE4-TR > apoE3-TR = apoE-KO > apoE2-TR), and that comparable doses of unaggregated Abeta1-42 did not affect LTP. These data provide a novel link among apoE isoform, Abeta1-42, and a functional cellular model of memory. In this model, apoE4 confers a gain of negative function synergistic with Abeta1-42, apoE2 is protective, and the apoE-Abeta interaction is specific to oligomeric Abeta1-42.

Duke Scholars

Published In

Neurobiol Dis

DOI

ISSN

0969-9961

Publication Date

February 2005

Volume

18

Issue

1

Start / End Page

75 / 82

Location

United States

Related Subject Headings

  • Protein Isoforms
  • Protein Conformation
  • Peptide Fragments
  • Organ Culture Techniques
  • Neuroprotective Agents
  • Neurology & Neurosurgery
  • Molecular Weight
  • Mice, Transgenic
  • Mice, Knockout
  • Mice
 

Citation

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Trommer, B. L., Shah, C., Yun, S. H., Gamkrelidze, G., Pasternak, E. S., Stine, W. B., … LaDu, M. J. (2005). ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42. Neurobiol Dis, 18(1), 75–82. https://doi.org/10.1016/j.nbd.2004.08.011
Trommer, Barbara L., Chirag Shah, Sung Hwan Yun, Georgi Gamkrelidze, Emily S. Pasternak, W Blaine Stine, Arlene Manelli, Patrick Sullivan, Joseph F. Pasternak, and Mary Jo LaDu. “ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42.Neurobiol Dis 18, no. 1 (February 2005): 75–82. https://doi.org/10.1016/j.nbd.2004.08.011.
Trommer BL, Shah C, Yun SH, Gamkrelidze G, Pasternak ES, Stine WB, et al. ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42. Neurobiol Dis. 2005 Feb;18(1):75–82.
Trommer, Barbara L., et al. “ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42.Neurobiol Dis, vol. 18, no. 1, Feb. 2005, pp. 75–82. Pubmed, doi:10.1016/j.nbd.2004.08.011.
Trommer BL, Shah C, Yun SH, Gamkrelidze G, Pasternak ES, Stine WB, Manelli A, Sullivan P, Pasternak JF, LaDu MJ. ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42. Neurobiol Dis. 2005 Feb;18(1):75–82.
Journal cover image

Published In

Neurobiol Dis

DOI

ISSN

0969-9961

Publication Date

February 2005

Volume

18

Issue

1

Start / End Page

75 / 82

Location

United States

Related Subject Headings

  • Protein Isoforms
  • Protein Conformation
  • Peptide Fragments
  • Organ Culture Techniques
  • Neuroprotective Agents
  • Neurology & Neurosurgery
  • Molecular Weight
  • Mice, Transgenic
  • Mice, Knockout
  • Mice