Home › Research › TREM2 and immune genetics
TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways
Wang S, Sudan R, Peng V, Zhou Y, Du S, Yuede CM, Lei T, Hou J et al.. Cell, 2022-10-01
Topic: Brain proteins, microglia and lab models
Genetic studies have highlighted microglia as pivotal in orchestrating Alzheimer's disease (AD). Microglia that adhere to Aβ plaques acquire a transcriptional signature, "disease-associated microglia" (DAM), which largely emanates from the TREM2-DAP12 receptor complex that transmits intracellular signals through the protein tyrosine kinase SYK. The human TREM2 R47H variant associated with high AD risk fails to activate microglia via SYK.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Wang, S., Sudan, R., Peng, V., Zhou, Y., Du, S., Yuede, C. M., et al. (2022). TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways. Cell. https://doi.org/10.1016/j.cell.2022.09.033
Vancouver
Wang S, Sudan R, Peng V, Zhou Y, Du S, Yuede CM, et al. TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways. Cell. 2022. doi:10.1016/j.cell.2022.09.033. PMID: 36306735.
BibTeX
@article{wang2022-36306735,
author = {Wang, S. and Sudan, R. and Peng, V. and Zhou, Y. and Du, S. and Yuede, C. M. and Lei, T. and Hou, J. and others},
title = {{TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways}},
journal = {Cell},
year = {2022},
doi = {10.1016/j.cell.2022.09.033},
pmid = {36306735},
url = {https://doi.org/10.1016/j.cell.2022.09.033}
}
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.
Key findings
- Microglia that adhere to Aβ plaques acquire a transcriptional signature, "disease-associated microglia" (DAM), which largely emanates from the TREM2-DAP12 receptor complex that transmits intracellular signals through the protein tyrosine kinase SYK.
- The human TREM2 R47H variant associated with high AD risk fails to activate microglia via SYK.
- We found that SYK-deficient microglia cannot encase Aβ plaques, accelerating brain pathology and behavioral deficits.
- SYK deficiency impaired the PI3K-AKT-GSK-3β-mTOR pathway, incapacitating anabolic support required for attaining the DAM profile.
Why it matters
In mice, microglia lacking the SYK protein could not encase amyloid plaques, which worsened brain pathology and behavioral deficits. This identifies a signaling pathway involved in microglial response to amyloid, but it is animal work and not a treatment.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 58/100
Published in a peer-reviewed 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 | 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 | 3 / 5 | 2022 — within 6 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 463 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 77.2 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 5 / 6 | Cited 23.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 19 other studies in this library |
| Still being cited | 4 / 4 | Cited 389 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) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36306735) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 58 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Related
Studies in the library that share something with this one. The line above each title says what.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 26.
Later studies that cite this one
19 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in TREM2 and immune genetics
Also tagged “r47h”
363 studies in the library carry the topic tag “r47h”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 363 tagged studies.