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TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model
Wang Y, Cella M, Mallinson K, Ulrich JD, Young KL, Robinette ML, Gilfillan S, Krishnan GM et al.. Cell, 2015-02-26
Topic: Brain proteins, microglia and lab models
Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor that triggers intracellular protein tyrosine phosphorylation. Recent genome-wide association studies have shown that a rare R47H mutation of TREM2 correlates with a substantial increase in the risk of developing Alzheimer's disease (AD). To address the basis for this genetic association, we studied TREM2 deficiency in the 5XFAD mouse model of AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Wang, Y., Cella, M., Mallinson, K., Ulrich, J. D., Young, K. L., Robinette, M. L., et al. (2015). TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model. Cell. https://doi.org/10.1016/j.cell.2015.01.049
Vancouver
Wang Y, Cella M, Mallinson K, Ulrich JD, Young KL, Robinette ML, et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model. Cell. 2015. doi:10.1016/j.cell.2015.01.049. PMID: 25728668.
BibTeX
@article{wang2015-25728668,
author = {Wang, Y. and Cella, M. and Mallinson, K. and Ulrich, J. D. and Young, K. L. and Robinette, M. L. and Gilfillan, S. and Krishnan, G. M. and others},
title = {{TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model}},
journal = {Cell},
year = {2015},
doi = {10.1016/j.cell.2015.01.049},
pmid = {25728668},
url = {https://doi.org/10.1016/j.cell.2015.01.049}
}
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Key findings
- Recent genome-wide association studies have shown that a rare R47H mutation of TREM2 correlates with a substantial increase in the risk of developing Alzheimer's disease (AD).
- To address the basis for this genetic association, we studied TREM2 deficiency in the 5XFAD mouse model of AD.
- We found that TREM2 deficiency and haploinsufficiency augment β-amyloid (Aβ) accumulation due to a dysfunctional response of microglia, which fail to cluster around Aβ plaques and become apoptotic.
- We further demonstrate that TREM2 senses a broad array of anionic and zwitterionic lipids known to associate with fibrillar Aβ in lipid membranes and to be exposed on the surface of damaged neurons.
Why it matters
A rare TREM2 gene change (R47H) is linked to a higher risk of Alzheimer's, so this study removed TREM2, fully or partly, in a mouse model of the disease (5XFAD). With less TREM2, more amyloid built up because the brain's immune cells (microglia) failed to gather around plaques and died, and the authors report that TREM2 senses lipids found with amyloid and on damaged nerve cells. This is mouse work that tested TREM2 loss rather than the R47H variant itself, and it does not test any treatment or show an effect in people.
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Study details
- Evidence strengthLow
How this study scored 62/100
Published in a peer-reviewed 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 | 7 / 10 | Tier 3 — peer-reviewed journal (Cell) |
| Journal's citation record | 4 / 4 | Cell: journal h-index 1,220 (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 | 2015 — 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 1,731 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 133.2 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 6 / 6 | Cited 55.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 6 / 6 | Cited by 289 other studies in this library |
| Still being cited | 4 / 4 | Cited 480 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Marco Colonna: h-index 172 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25728668) |
| Free to read | 2 / 2 | Free to read |
| Total | 62 / 100 | — |
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