Home › Research › TREM2 and immune genetics
Alzheimer's disease-associated TREM2 variants exhibit either decreased or increased ligand-dependent activation
Song W, Hooli B, Mullin K, Jin SC, Cella M, Ulland TK, Wang Y, Tanzi RE et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2016-08-09
Topic: Brain proteins, microglia and lab models
Introduction TREM2 is a lipid-sensing activating receptor on microglia known to be important for Alzheimer's disease (AD), but whether it plays a beneficial or detrimental role in disease pathogenesis is controversial. Methods We analyzed AD risk of TREM2 variants in the NIMH AD Genetics Initiative Study and AD Sequencing Project. We compared each variant's risk and functional impact by a reporter assay.
Key findings
- Methods We analyzed AD risk of TREM2 variants in the NIMH AD Genetics Initiative Study and AD Sequencing Project.
- We compared each variant's risk and functional impact by a reporter assay.
- Finally, we analyzed expression of TREM2 on human monocytes.
- Results We provide more evidence for increased AD risk associated with several TREM2 variants, and show that these variants decreased or markedly increased binding to TREM2 ligands.
Why it matters
This study found that Alzheimer's-associated TREM2 variants either decreased or markedly increased binding to TREM2 ligands, while confirming increased Alzheimer's risk for several variants. It is a genetic and lab-based analysis and does not test any treatment.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 55/100
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 (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (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 | 2017 — 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 | 5 / 7 | Cited 299 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 27.2 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 4 / 6 | Cited 9.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 60 other studies in this library |
| Still being cited | 3 / 4 | Cited 73 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Marco Colonna: h-index 172 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27520774) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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
Song, W., Hooli, B., Mullin, K., Jin, S. C., Cella, M., Ulland, T. K., et al. (2017). Alzheimer's disease-associated TREM2 variants exhibit either decreased or increased ligand-dependent activation. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1016/j.jalz.2016.07.004
Vancouver
Song W, Hooli B, Mullin K, Jin SC, Cella M, Ulland TK, et al. Alzheimer's disease-associated TREM2 variants exhibit either decreased or increased ligand-dependent activation. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2017. doi:10.1016/j.jalz.2016.07.004. PMID: 27520774.
BibTeX
@article{song2017-27520774,
author = {Song, W. and Hooli, B. and Mullin, K. and Jin, S. C. and Cella, M. and Ulland, T. K. and Wang, Y. and Tanzi, R. E. and others},
title = {{Alzheimer's disease-associated TREM2 variants exhibit either decreased or increased ligand-dependent activation}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2017},
doi = {10.1016/j.jalz.2016.07.004},
pmid = {27520774},
url = {https://doi.org/10.1016/j.jalz.2016.07.004}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 17.
Later studies that cite this one
60 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.