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Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer's disease model
Zhong L, Xu Y, Zhuo R, Wang T, Wang K, Huang R, Wang D, Gao Y et al.. Nature communications, 2019-03-25
Topic: Brain proteins, microglia and lab models
Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor genetically linked to the risk for Alzheimer's disease (AD). A proteolytic product, soluble TREM2 (sTREM2), is abundant in the cerebrospinal fluid and its levels positively correlate with neuronal injury markers. To gain insights into the pathological roles of sTREM2, we studied sTREM2 in the brain of 5xFAD mice, a model of AD, by direct stereotaxic injection of recombinant sTREM2 protein or by adeno-associated virus (AAV)-mediated expression.
Key findings
- A proteolytic product, soluble TREM2 (sTREM2), is abundant in the cerebrospinal fluid and its levels positively correlate with neuronal injury markers.
- To gain insights into the pathological roles of sTREM2, we studied sTREM2 in the brain of 5xFAD mice, a model of AD, by direct stereotaxic injection of recombinant sTREM2 protein or by adeno-associated virus (AAV)-mediated expression.
- We found that sTREM2 reduces amyloid plaque load and rescues functional deficits of spatial memory and long-term potentiation.
- Importantly, sTREM2 enhances microglial proliferation, migration, clustering in the vicinity of amyloid plaques and the uptake and degradation of Aβ.
Why it matters
In 5xFAD mice, a model of Alzheimer's disease, raising soluble TREM2 in the brain by direct injection or by a viral vector "reduces amyloid plaque load and rescues functional deficits of spatial memory and long-term potentiation". The study also reports that soluble TREM2 increased microglial proliferation, migration and clustering around plaques, and their "uptake and degradation of Aβ". These are mouse results with no sample sizes or effect sizes given here. They do not show that soluble TREM2, or any TREM2-targeting drug, treats or prevents Alzheimer's disease in people.
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Study details
- Evidence strengthLow
How this study scored 57/100
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 | 2 / 5 | 2019 — 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 373 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 41.4 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 4 / 6 | Cited 15.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 45 other studies in this library |
| Still being cited | 3 / 4 | Cited 133 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 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30911003) |
| Free to read | 2 / 2 | Free to read |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41467-019-09118-9
- PubMed: 30911003
- 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
Zhong, L., Xu, Y., Zhuo, R., Wang, T., Wang, K., Huang, R., et al. (2019). Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer's disease model. Nature communications. https://doi.org/10.1038/s41467-019-09118-9
Vancouver
Zhong L, Xu Y, Zhuo R, Wang T, Wang K, Huang R, et al. Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer's disease model. Nature communications. 2019. doi:10.1038/s41467-019-09118-9. PMID: 30911003.
BibTeX
@article{zhong2019-30911003,
author = {Zhong, L. and Xu, Y. and Zhuo, R. and Wang, T. and Wang, K. and Huang, R. and Wang, D. and Gao, Y. and others},
title = {{Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer's disease model}},
journal = {Nature communications},
year = {2019},
doi = {10.1038/s41467-019-09118-9},
pmid = {30911003},
url = {https://doi.org/10.1038/s41467-019-09118-9}
}
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