Home › Research › TREM2 and immune genetics
Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer's disease
McQuade A, Kang YJ, Hasselmann J, Jairaman A, Sotelo A, Coburn M, Shabestari SK, Chadarevian JP et al.. Nature communications, 2020-10-23
Topic: Brain proteins, microglia and lab models
The discovery of TREM2 as a myeloid-specific Alzheimer's disease (AD) risk gene has accelerated research into the role of microglia in AD. While TREM2 mouse models have provided critical insight, the normal and disease-associated functions of TREM2 in human microglia remain unclear. To examine this question, we profile microglia differentiated from isogenic, CRISPR-modified TREM2-knockout induced pluripotent stem cell (iPSC) lines.
Key findings
- While TREM2 mouse models have provided critical insight, the normal and disease-associated functions of TREM2 in human microglia remain unclear.
- To examine this question, we profile microglia differentiated from isogenic, CRISPR-modified TREM2-knockout induced pluripotent stem cell (iPSC) lines.
- By combining transcriptomic and functional analyses with a chimeric AD mouse model, we find that TREM2 deletion reduces microglial survival, impairs phagocytosis of key substrates including APOE, and inhibits SDF-1α/CXCR4-mediated chemotaxis, culminating in an impaired response to beta-amyloid plaques in vivo.
- Single-cell sequencing of xenotransplanted human microglia further highlights a loss of disease-associated microglial (DAM) responses in human TREM2 knockout microglia that we validate by flow cytometry and immunohistochemistry.
Why it matters
Using human iPSC-derived microglia and a chimeric mouse model, this study found that deleting TREM2 reduced microglial survival and impaired phagocytosis. These are laboratory and animal findings and do not establish a treatment, cure, or prevention for Alzheimer's disease in humans.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 56/100
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 | 2020 — 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 357 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 44.6 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 4 / 6 | Cited 13.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 25 other studies in this library |
| Still being cited | 3 / 4 | Cited 195 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Mathew M. Blurton-Jones: h-index 57 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of California, Irvine: institution h-index 1,195 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33097708) |
| Free to read | 2 / 2 | Free to read |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/s41467-020-19227-5
- PubMed: 33097708
- 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
McQuade, A., Kang, Y. J., Hasselmann, J., Jairaman, A., Sotelo, A., Coburn, M., et al. (2020). Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer's disease. Nature communications. https://doi.org/10.1038/s41467-020-19227-5
Vancouver
McQuade A, Kang YJ, Hasselmann J, Jairaman A, Sotelo A, Coburn M, et al. Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer's disease. Nature communications. 2020. doi:10.1038/s41467-020-19227-5. PMID: 33097708.
BibTeX
@article{mcquade2020-33097708,
author = {McQuade, A. and Kang, Y. J. and Hasselmann, J. and Jairaman, A. and Sotelo, A. and Coburn, M. and Shabestari, S. K. and Chadarevian, J. P. and others},
title = {{Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer's disease}},
journal = {Nature communications},
year = {2020},
doi = {10.1038/s41467-020-19227-5},
pmid = {33097708},
url = {https://doi.org/10.1038/s41467-020-19227-5}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 35.
Later studies that cite this one
25 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.