ApoE isoform affects LTP in human targeted replacement mice
Trommer BL, Shah C, Yun SH, Gamkrelidze G, Pasternak ES, Ye GL, Sotak M, Sullivan PM et al.. Neuroreport, 2004-12-01
Topic: Brain proteins, microglia and lab models
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.
Key findings
- 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.
- 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.
Why it matters
In hippocampal slices from mice engineered to carry human APOE2, E3 or E4, long-term potentiation, a laboratory model of memory, was greater in mice with APOE3 than in those with APOE2 or APOE4. This is animal and tissue work that may help investigate how APOE forms affect susceptibility to memory impairment, but it does not yet show anything about treating people.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuroreport) |
| Journal's citation record | 2 / 4 | Neuroreport: journal h-index 242 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2004 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mice”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 124 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.2 citations a year over 24 year(s) since 2004 |
| Impact for its field and year | 2 / 6 | Cited 2.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 1 / 4 | Cited 12 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Mary Jo LaDu: h-index 60 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Northwestern University: institution h-index 1,592 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15570172) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 41 / 100 | — |
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May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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APA 7th
Trommer, B. L., Shah, C., Yun, S. H., Gamkrelidze, G., Pasternak, E. S., Ye, G. L., et al. (2004). ApoE isoform affects LTP in human targeted replacement mice. Neuroreport. https://doi.org/10.1097/00001756-200412030-00020
Vancouver
Trommer BL, Shah C, Yun SH, Gamkrelidze G, Pasternak ES, Ye GL, et al. ApoE isoform affects LTP in human targeted replacement mice. Neuroreport. 2004. doi:10.1097/00001756-200412030-00020. PMID: 15570172.
BibTeX
@article{trommer2004-15570172,
author = {Trommer, B. L. and Shah, C. and Yun, S. H. and Gamkrelidze, G. and Pasternak, E. S. and Ye, G. L. and Sotak, M. and Sullivan, P. M. and others},
title = {{ApoE isoform affects LTP in human targeted replacement mice}},
journal = {Neuroreport},
year = {2004},
doi = {10.1097/00001756-200412030-00020},
pmid = {15570172},
url = {https://doi.org/10.1097/00001756-200412030-00020}
}
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