Home › Research › TREM2 and immune genetics
Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer's R47H mutant increases Aβ aggregation
Vilalta A, Zhou Y, Sevalle J, Griffin JK, Satoh K, Allendorf DH, De S, Puigdellívol M et al.. The Journal of biological chemistry, 2021-01-01
Topic: Brain proteins, microglia and lab models
TREM2 is a pattern recognition receptor, expressed on microglia and myeloid cells, detecting lipids and Aβ and inducing an innate immune response. Missense mutations (e.g., R47H) of TREM2 increase risk of Alzheimer's disease (AD). The soluble ectodomain of wild-type TREM2 (sTREM2) has been shown to protect against AD in vivo, but the underlying mechanisms are unclear.
Key findings
- Missense mutations (e.g., R47H) of TREM2 increase risk of Alzheimer's disease (AD).
- The soluble ectodomain of wild-type TREM2 (sTREM2) has been shown to protect against AD in vivo, but the underlying mechanisms are unclear.
- We show that Aβ oligomers bind to cellular TREM2, inducing shedding of the sTREM2 domain.
- Wild-type sTREM2 bound to Aβ oligomers (measured by single-molecule imaging, dot blots, and Bio-Layer Interferometry) inhibited Aβ oligomerization and disaggregated preformed Aβ oligomers and protofibrils (measured by transmission electron microscopy, dot blots, and size-exclusion chromatography).
Why it matters
Wild-type soluble TREM2 blocked Aβ aggregation and broke up preformed Aβ oligomers, while the Alzheimer's-linked R47H mutant increased Aβ aggregation. This is laboratory work on mechanisms and does not yet show a treatment, cure, or prevention for Alzheimer's disease in people.
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 (The Journal of biological chemistry) |
| Journal's citation record | 4 / 4 | Journal of Biological Chemistry: journal h-index 780 (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 | 2021 — 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 | 12.0 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 7.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 2 / 4 | Cited 40 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Guy Charles Brown: h-index 88 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33823153) |
| 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: 10.1016/j.jbc.2021.100631
- PubMed: 33823153
- Original source →
- Free full text: Journal of Biological Chemistry →
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
Vilalta, A., Zhou, Y., Sevalle, J., Griffin, J. K., Satoh, K., Allendorf, D. H., et al. (2021). Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer's R47H mutant increases Aβ aggregation. The Journal of biological chemistry. https://doi.org/10.1016/j.jbc.2021.100631
Vancouver
Vilalta A, Zhou Y, Sevalle J, Griffin JK, Satoh K, Allendorf DH, et al. Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer's R47H mutant increases Aβ aggregation. The Journal of biological chemistry. 2021. doi:10.1016/j.jbc.2021.100631. PMID: 33823153.
BibTeX
@article{vilalta2021-33823153,
author = {Vilalta, A. and Zhou, Y. and Sevalle, J. and Griffin, J. K. and Satoh, K. and Allendorf, D. H. and De, S. and Puigdellívol, M. and others},
title = {{Wild-type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer's R47H mutant increases Aβ aggregation}},
journal = {The Journal of biological chemistry},
year = {2021},
doi = {10.1016/j.jbc.2021.100631},
pmid = {33823153},
url = {https://doi.org/10.1016/j.jbc.2021.100631}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 28.
Later studies that cite this one
11 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 “macrophages”
363 studies in the library carry the topic tag “macrophages”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 363 tagged studies.