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TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration
Zhong L, Sheng X, Wang W, Li Y, Zhuo R, Wang K, Zhang L, Hu DD et al.. Immunity, 2023-07-12
Topic: Brain proteins, microglia and lab models
Triggering receptor expressed on myeloid cells 2 (TREM2) is strongly linked to Alzheimer's disease (AD) risk, but its functions are not fully understood. Here, we found that TREM2 specifically attenuated the activation of classical complement cascade via high-affinity binding to its initiator C1q. In the human AD brains, the formation of TREM2-C1q complexes was detected, and the increased density of the complexes was associated with lower deposition of C3 but higher amounts of synaptic proteins.
Key findings
- Here, we found that TREM2 specifically attenuated the activation of classical complement cascade via high-affinity binding to its initiator C1q.
- In the human AD brains, the formation of TREM2-C1q complexes was detected, and the increased density of the complexes was associated with lower deposition of C3 but higher amounts of synaptic proteins.
- In mice expressing mutant human tau, Trem2 haploinsufficiency increased complement-mediated microglial engulfment of synapses and accelerated synaptic loss.
- Administration of a 41-amino-acid TREM2 peptide, which we identified to be responsible for TREM2 binding to C1q, rescued synaptic impairments in AD mouse models.
Why it matters
This study found that TREM2 binds complement C1q and attenuates classical complement activation, and that in mice with mutant human tau, reduced Trem2 increased complement-mediated microglial engulfment of synapses and accelerated synaptic loss. This is largely animal and human brain tissue work and does not establish a treatment, cure or prevention for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 51/100
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 (Immunity) |
| Journal's citation record | 4 / 4 | Immunity: journal h-index 567 (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 | 2023 — 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 | 5 / 7 | Cited 164 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 32.8 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 4 / 6 | Cited 13.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 3 / 4 | Cited 152 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Xiao‐Fen Chen: h-index 29 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37442133) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
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
Zhong, L., Sheng, X., Wang, W., Li, Y., Zhuo, R., Wang, K., et al. (2023). TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration. Immunity. https://doi.org/10.1016/j.immuni.2023.06.016
Vancouver
Zhong L, Sheng X, Wang W, Li Y, Zhuo R, Wang K, et al. TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration. Immunity. 2023. doi:10.1016/j.immuni.2023.06.016. PMID: 37442133.
BibTeX
@article{zhong2023-37442133,
author = {Zhong, L. and Sheng, X. and Wang, W. and Li, Y. and Zhuo, R. and Wang, K. and Zhang, L. and Hu, D. D. and others},
title = {{TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration}},
journal = {Immunity},
year = {2023},
doi = {10.1016/j.immuni.2023.06.016},
pmid = {37442133},
url = {https://doi.org/10.1016/j.immuni.2023.06.016}
}
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