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Soluble TREM2 ameliorates tau phosphorylation and cognitive deficits through activating transgelin-2 in Alzheimer's disease
Zhang X, Tang L, Yang J, Meng L, Chen J, Zhou L, Wang J, Xiong M et al.. Nature communications, 2023-10-21
Topic: Brain proteins, microglia and lab models
Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein that is predominantly expressed by microglia in the brain. The proteolytic shedding of TREM2 results in the release of soluble TREM2 (sTREM2), which is increased in the cerebrospinal fluid of patients with Alzheimer's disease (AD). It remains unknown whether sTREM2 regulates the pathogenesis of AD.
Key findings
- The proteolytic shedding of TREM2 results in the release of soluble TREM2 (sTREM2), which is increased in the cerebrospinal fluid of patients with Alzheimer's disease (AD).
- It remains unknown whether sTREM2 regulates the pathogenesis of AD.
- Here we identified transgelin-2 (TG2) expressed on neurons as the receptor for sTREM2.
- The microglia-derived sTREM2 binds to TG2, induces RhoA phosphorylation at S188, and deactivates the RhoA-ROCK-GSK3β pathway, ameliorating tau phosphorylation.
Why it matters
In this work, soluble TREM2 released by microglia bound to a neuronal receptor called transgelin-2 and reduced tau phosphorylation and cognitive deficits. These findings point to a possible mechanism for lowering tau damage, but they come from experimental models and do not yet establish a treatment for patients.
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Study details
- Evidence strengthLow
How this study scored 52/100
Published in a leading specialty 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 | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| Journal's citation record | 4 / 4 | Nature Communications: journal h-index 747 (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 | 4 / 7 | Cited 84 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.8 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 4 / 6 | Cited 12.3× 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 83 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Zhentao Zhang: h-index 54 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Wuhan University: institution h-index 808 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37865646) |
| Free to read | 2 / 2 | Free to read |
| Total | 52 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41467-023-42505-x
- PubMed: 37865646
- Original source →
- Free full text: Nature Communications →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Zhang, X., Tang, L., Yang, J., Meng, L., Chen, J., Zhou, L., et al. (2023). Soluble TREM2 ameliorates tau phosphorylation and cognitive deficits through activating transgelin-2 in Alzheimer's disease. Nature communications. https://doi.org/10.1038/s41467-023-42505-x
Vancouver
Zhang X, Tang L, Yang J, Meng L, Chen J, Zhou L, et al. Soluble TREM2 ameliorates tau phosphorylation and cognitive deficits through activating transgelin-2 in Alzheimer's disease. Nature communications. 2023. doi:10.1038/s41467-023-42505-x. PMID: 37865646.
BibTeX
@article{zhang2023-37865646,
author = {Zhang, X. and Tang, L. and Yang, J. and Meng, L. and Chen, J. and Zhou, L. and Wang, J. and Xiong, M. and others},
title = {{Soluble TREM2 ameliorates tau phosphorylation and cognitive deficits through activating transgelin-2 in Alzheimer's disease}},
journal = {Nature communications},
year = {2023},
doi = {10.1038/s41467-023-42505-x},
pmid = {37865646},
url = {https://doi.org/10.1038/s41467-023-42505-x}
}
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