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Reversing EphB2 depletion rescues cognitive functions in Alzheimer model
Cissé M, Halabisky B, Harris J, Devidze N, Dubal DB, Sun B, Orr A, Lotz G et al.. Nature, 2010-11-28
Topic: Brain proteins, microglia and lab models
Amyloid-β oligomers may cause cognitive deficits in Alzheimer's disease by impairing neuronal NMDA-type glutamate receptors, whose function is regulated by the receptor tyrosine kinase EphB2. Here we show that amyloid-β oligomers bind to the fibronectin repeats domain of EphB2 and trigger EphB2 degradation in the proteasome. To determine the pathogenic importance of EphB2 depletions in Alzheimer's disease and related models, we used lentiviral constructs to reduce or increase neuronal expression of EphB2 in memory centres of the mouse brain.
Key findings
- Here we show that amyloid-β oligomers bind to the fibronectin repeats domain of EphB2 and trigger EphB2 degradation in the proteasome.
- To determine the pathogenic importance of EphB2 depletions in Alzheimer's disease and related models, we used lentiviral constructs to reduce or increase neuronal expression of EphB2 in memory centres of the mouse brain.
- In nontransgenic mice, knockdown of EphB2 mediated by short hairpin RNA reduced NMDA receptor currents and impaired long-term potentiation in the dentate gyrus, which are important for memory formation.
- Increasing EphB2 expression in the dentate gyrus of human amyloid precursor protein transgenic mice reversed deficits in NMDA receptor-dependent long-term potentiation and memory impairments.
Why it matters
In mice, reducing EphB2 impaired memory-related brain functions, and increasing EphB2 rescued cognitive functions in an Alzheimer's model. This is an animal study, so it does not show that targeting EphB2 would treat, cure, or prevent Alzheimer's disease in people.
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Study details
- Evidence strengthLow
How this study scored 56/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature) |
| Journal's citation record | 4 / 4 | Nature: journal h-index 1,841 (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 | 2011 — within 20 year(s) of the newest study here |
| 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 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 431 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 25.4 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 5 / 6 | Cited 23.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 3 / 4 | Cited 50 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Lennart Mucke: h-index 108 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21113149) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
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Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Cissé, M., Halabisky, B., Harris, J., Devidze, N., Dubal, D. B., Sun, B., et al. (2011). Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. Nature. https://doi.org/10.1038/nature09635
Vancouver
Cissé M, Halabisky B, Harris J, Devidze N, Dubal DB, Sun B, et al. Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. Nature. 2011. doi:10.1038/nature09635. PMID: 21113149.
BibTeX
@article{cisse2011-21113149,
author = {Cissé, M. and Halabisky, B. and Harris, J. and Devidze, N. and Dubal, D. B. and Sun, B. and Orr, A. and Lotz, G. and others},
title = {{Reversing EphB2 depletion rescues cognitive functions in Alzheimer model}},
journal = {Nature},
year = {2011},
doi = {10.1038/nature09635},
pmid = {21113149},
url = {https://doi.org/10.1038/nature09635}
}
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