Cited by 82Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchDementia and Cognitive Impairment Research

ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-β1–42

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Trommer, Barbara L., Shah, Chirag, Yun, Sung Hwan, Gamkrelidze, Georgi, Pasternak, Emily S., Blaine Stine, W., Manelli, Arlene, Sullivan, Patrick +2 more·2005·Neurobiology of Disease

Abstract

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.

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Crossref · 10.1016/j.nbd.2004.08.011

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Authors
Trommer, B. L., Shah, C., Yun, S. H., Gamkrelidze, G., Pasternak, E. S., Blaine Stine, W., Manelli, A., Sullivan, P., Pasternak, J. F., & LaDu, M. J.
Affiliations
  • Northwestern University (US)
  • Duke University (US)
Corresponding author
Trommer, Barbara L.
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2005-02
Volume
18
Issue
1
Pages
75-82
ISSN
0969-9961 (ISSN-L)
OpenAlex
W2055766521
Cited by
82
References
72
Citations by year
2025: 1 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 4 · 2013: 1 · 2012: 5
FWCI
3.08
Type
journal article
Language
en
Open access
Locations
  • Neurobiology of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute on Aging (AG18121)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
apolipoprotein E isoforms, amyloid-beta 42, amyloid-beta oligomers, long-term potentiation, Alzheimer's disease, APOE ε4, APOE2, APOE3, hippocampus, memory
MeSH terms
Alzheimer Disease, Animals, Apolipoproteins E, Cell Survival, Hippocampus, Male, Mice, Transgenic, Molecular Weight, Organ Culture Techniques, Peptide Fragments, Protein Conformation, Amyloid beta-Peptides, Long-Term Potentiation, Mice, Knockout, Neuroprotective Agents, Protein Isoforms, Mice, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2

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