ApoE isoform affects LTP in human targeted replacement mice
Abstract
Inheritance of the epsilon4 allele for apolipoprotein E (apoE) increases the risk of Alzheimer disease and memory impairment, whereas epsilon2 decreases these risks compared with the most common epsilon3 allele, but the mechanism for these effects is unknown. Long-term potentiation (LTP) is an experimentally induced increase in synaptic efficacy that models memory. Using hippocampal slices from wild type (WT), apoE knockout (apoE-KO), and targeted replacement mice expressing human apoE2, E3, or E4 (apoE-TR) we found that although all strains had comparable basal synaptic transmission, LTP was significantly greater in WT and apoE3-TR than in apoE-KO, apoE2-TR or apoE4-TR. This novel system may be used to investigate the mechanisms of apoE isoform dependent modulation of susceptibility to memory impairment.
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The APOE2hAβ LTP finding is consistent with observations reported in APOE2-carrying mice but appears paradoxical given APOE2's typical association with neuroprotection in AD.
“This finding is consistent with observations reported in APOE2-carrying mice [82], but appears paradoxical given APOE2’s typical association with neuroprotection in AD [83, 84].”
Long-term potentiation (LTP) was reduced in apoE4 knock-in mice, compared with apoE3 mice.
“long-term potentiation (LTP) was reduced in apoE4 knock-in mice, compared with apoE3 mice (Trommer et al., 2004)”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as Trommer et al., 2004
LTP in apoE2 knock-in mice was significantly less than apoE3 mice and comparable with apoE4 mice.
“Surprisingly, LTP in apoE2 knock-in mice was significantly less than apoE3 mice and comparable with apoE4 mice (Trommer et al., 2004).”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as Trommer et al., 2004
Some phenotypic differences observed with apoE transgenic mouse models have been replicated with apoE knock-in mouse models.
“Some phenotypic differences observed with apoE transgenic mouse models have been replicated with apoE knock-in mouse models (Bour et al., 2008; Grootendorst et al., 2005; Trommer et al., 2004; Wang et al., 2005).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Trommer et al., 2004
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“This finding is consistent with observations reported in APOE2-carrying mice [82], but appears paradoxical given APOE2’s typical association with neuroprotection in AD [83, 84].”
Result
- Authors
- Trommer, B. L., Shah, C., Yun, S. H., Gamkrelidze, G., Pasternak, E. S., Ye, G. L., Sotak, M., Sullivan, P. M., Pasternak, J. F., & LaDu, M. J.
- Affiliations
- Northwestern University (US)
- Neurology, Inc (US)
- Duke University (US)
- Venue
- NeuroReport
- Published
- 2004-12
- Volume
- 15
- Issue
- 17
- Pages
- 2655-2658
- ISSN
- 0959-4965 (ISSN-L)
- OpenAlex
- W2117437037
- Cited by
- 124
- References
- 25
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 9 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 7 · 2016: 6 · 2015: 2 · 2014: 10 · 2013: 10 · 2012: 5
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroreport (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG019121, AG 19121)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- apolipoprotein E, APOE isoforms, long-term potentiation, Alzheimer's disease, memory impairment, hippocampus, synaptic transmission, targeted replacement mice, ApoE-deficient mice, APOE ε4, APOE2, APOE3
- MeSH terms
- Analysis of Variance, Animals, Apolipoproteins E, Electric Stimulation, Hippocampus, Humans, Mice, Inbred C57BL, Mice, Transgenic, Long-Term Potentiation, Protein Isoforms, Mice, In Vitro Techniques
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