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TREM2 and sTREM2 in Alzheimer's disease: from mechanisms to therapies
Zhang L, Xiang X, Li Y, Bu G, Chen XF.. Molecular neurodegeneration, 2025-04-17
Topic: Brain proteins, microglia and lab models
Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor predominantly expressed by microglia in the brain. Recent studies have established TREM2 as a central immune signaling hub in neurodegeneration, where it triggers immune responses upon sensing pathological development and tissue damages. TREM2 binds diverse ligands and activates downstream pathways that regulate microglial phagocytosis, inflammatory responses, and metabolic reprogramming.
Key findings
- Recent studies have established TREM2 as a central immune signaling hub in neurodegeneration, where it triggers immune responses upon sensing pathological development and tissue damages.
- TREM2 binds diverse ligands and activates downstream pathways that regulate microglial phagocytosis, inflammatory responses, and metabolic reprogramming.
- Interestingly, TREM2 exists both in its membrane-bound form and as a soluble variant (sTREM2), that latter is generated through proteolytic shedding or alternative splicing and can be detected in cerebrospinal fluid and plasma.
- Emerging clinical and preclinical evidence underscores the potential of TREM2 and sTREM2 as diagnostic biomarkers and therapeutic targets in Alzheimer's disease (AD).
Why it matters
This review describes TREM2 as an immune signaling hub in neurodegeneration and covers its membrane-bound and soluble forms and downstream pathways. It is a review of mechanisms and does not report a treatment, cure or prevention for Alzheimer's disease.
New to this subject? Start with our plain-English guide: Genetics →
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 (Molecular neurodegeneration) |
| Journal's citation record | 2 / 4 | Molecular Neurodegeneration: journal h-index 164 (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 | 4 / 5 | 2025 — within 3 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 66 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 5 / 6 | Cited 20.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 3 / 4 | Cited 66 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 | Chinese Academy of Sciences: institution h-index 1,801 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40247363) |
| Free to read | 2 / 2 | Free to read |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1186/s13024-025-00834-z
- PubMed: 40247363
- Original source →
- Free full text: Molecular Neurodegeneration →
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. Check the citation against the original before you use it.
APA 7th
Zhang, L., Xiang, X., Li, Y., Bu, G., & Chen, X. F. (2025). TREM2 and sTREM2 in Alzheimer's disease: from mechanisms to therapies. Molecular neurodegeneration. https://doi.org/10.1186/s13024-025-00834-z
Vancouver
Zhang L, Xiang X, Li Y, Bu G, Chen XF. TREM2 and sTREM2 in Alzheimer's disease: from mechanisms to therapies. Molecular neurodegeneration. 2025. doi:10.1186/s13024-025-00834-z. PMID: 40247363.
BibTeX
@article{zhang2025-40247363,
author = {Zhang, L. and Xiang, X. and Li, Y. and Bu, G. and Chen, X. F.},
title = {{TREM2 and sTREM2 in Alzheimer's disease: from mechanisms to therapies}},
journal = {Molecular neurodegeneration},
year = {2025},
doi = {10.1186/s13024-025-00834-z},
pmid = {40247363},
url = {https://doi.org/10.1186/s13024-025-00834-z}
}
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