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Microglia TREM2R47H Alzheimer-linked variant enhances excitatory transmission and reduces LTP via increased TNF-α levels
Ren S, Yao W, Tambini MD, Yin T, Norris KA, D'Adamio L.. eLife, 2020-06-24
Topic: Brain proteins, microglia and lab models
To study the mechanisms by which the p.R47H variant of the microglia gene and Alzheimer's disease (AD) risk factor TREM2 increases dementia risk, we created Trem2 R47H KI rats. Trem2 R47H rats were engineered to produce human Aβ to define human-Aβ-dependent and -independent pathogenic mechanisms triggered by this variant. Interestingly, pre- and peri-adolescent Trem2 R47H rats present increased brain concentrations of TNF-α, augmented glutamatergic transmission, suppression of Long-term-Potentiation (LTP), an electrophysiological surrogate of learning and memory, but normal Aβ levels.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Ren, S., Yao, W., Tambini, M. D., Yin, T., Norris, K. A., & D'Adamio, L. (2020). Microglia TREM2R47H Alzheimer-linked variant enhances excitatory transmission and reduces LTP via increased TNF-α levels. eLife. https://doi.org/10.7554/elife.57513
Vancouver
Ren S, Yao W, Tambini MD, Yin T, Norris KA, D'Adamio L. Microglia TREM2R47H Alzheimer-linked variant enhances excitatory transmission and reduces LTP via increased TNF-α levels. eLife. 2020. doi:10.7554/elife.57513. PMID: 32579116.
BibTeX
@article{ren2020-32579116,
author = {Ren, S. and Yao, W. and Tambini, M. D. and Yin, T. and Norris, K. A. and D'Adamio, L.},
title = {{Microglia TREM2R47H Alzheimer-linked variant enhances excitatory transmission and reduces LTP via increased TNF-α levels}},
journal = {eLife},
year = {2020},
doi = {10.7554/elife.57513},
pmid = {32579116},
url = {https://doi.org/10.7554/elife.57513}
}
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Key findings
- Trem2 R47H rats were engineered to produce human Aβ to define human-Aβ-dependent and -independent pathogenic mechanisms triggered by this variant.
- Interestingly, pre- and peri-adolescent Trem2 R47H rats present increased brain concentrations of TNF-α, augmented glutamatergic transmission, suppression of Long-term-Potentiation (LTP), an electrophysiological surrogate of learning and memory, but normal Aβ levels.
- Acute reduction of TNF-α activity with a neutralizing anti-TNF-α antibody occludes the boost in amplitude of glutamatergic transmission and LTP suppression observed in young Trem2 R47H/R47H rats.
- Thus, the microglia-specific pathogenic Trem2 variant boosts glutamatergic neuronal transmission and suppresses LTP by increasing brain TNF-α concentrations, directly linking microglia to neuronal dysfunction.
Why it matters
In rats with the TREM2 R47H variant, increased TNF-α, enhanced excitatory transmission and reduced LTP occurred even with normal Aβ levels, and blocking TNF-α prevented some of these effects. This is animal research and does not yet provide a treatment for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 47/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (eLife) |
| Journal's citation record | 3 / 4 | ELife: journal h-index 311 (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 | 2 / 5 | 2020 — within 10 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 69 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.6 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 3 / 6 | Cited 3.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 27 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Luciano D'adamio: h-index 54 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Rutgers, The State University of New Jersey: institution h-index 1,147 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32579116) |
| Free to read | 2 / 2 | Free to read |
| Total | 47 / 100 | — |
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