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Rare TREM2 variants associated with Alzheimer's disease display reduced cell surface expression
Sirkis DW, Bonham LW, Aparicio RE, Geier EG, Ramos EM, Wang Q, Karydas A, Miller ZA et al.. Acta neuropathologica communications, 2016-09-02
Topic: Brain proteins, microglia and lab models
Rare variation in TREM2 has been associated with greater risk for Alzheimer's disease (AD). TREM2 encodes a cell surface receptor expressed on microglia and related cells, and the R47H variant associated with AD appears to affect the ability of TREM2 to bind extracellular ligands. In addition, other rare TREM2 mutations causing early-onset neurodegeneration are thought to impair cell surface expression.
Key findings
- TREM2 encodes a cell surface receptor expressed on microglia and related cells, and the R47H variant associated with AD appears to affect the ability of TREM2 to bind extracellular ligands.
- In addition, other rare TREM2 mutations causing early-onset neurodegeneration are thought to impair cell surface expression.
- Using a sequence kernel association (SKAT) analysis in two independent AD cohorts, we found significant enrichment of rare TREM2 variants not previously characterized at the protein level.
- Heterologous expression of the identified variants showed that novel variants S31F and R47C displayed significantly reduced cell surface expression.
Why it matters
Across two independent Alzheimer's disease cohorts, a gene-level test (SKAT) found rare TREM2 variants, not previously studied at the protein level, to be enriched in people with AD. When tested in cells, two newly described variants, S31F and R47C, put noticeably less TREM2 on the cell surface. This links more rare TREM2 changes to a possible loss of the receptor on microglia, but it is genetic and lab-based evidence: it does not give personal risk figures or show that raising TREM2 would treat or prevent Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 44/100
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 (Acta neuropathologica communications) |
| Journal's citation record | 1 / 4 | Acta Neuropathologica Communications: journal h-index 129 (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 | 1 / 5 | 2016 — within 20 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 62 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.2 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 3 / 6 | Cited 5.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 12 other studies in this library |
| Still being cited | 2 / 4 | Cited 17 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jennifer S. Yokoyama: h-index 49 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, Berkeley: institution h-index 2,012 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27589997) |
| Free to read | 2 / 2 | Free to read |
| Total | 44 / 100 | — |
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Read the original
- DOI: 10.1186/s40478-016-0367-7
- PubMed: 27589997
- Original source →
- Free full text: Acta Neuropathologica 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
Sirkis, D. W., Bonham, L. W., Aparicio, R. E., Geier, E. G., Ramos, E. M., Wang, Q., et al. (2016). Rare TREM2 variants associated with Alzheimer's disease display reduced cell surface expression. Acta neuropathologica communications. https://doi.org/10.1186/s40478-016-0367-7
Vancouver
Sirkis DW, Bonham LW, Aparicio RE, Geier EG, Ramos EM, Wang Q, et al. Rare TREM2 variants associated with Alzheimer's disease display reduced cell surface expression. Acta neuropathologica communications. 2016. doi:10.1186/s40478-016-0367-7. PMID: 27589997.
BibTeX
@article{sirkis2016-27589997,
author = {Sirkis, D. W. and Bonham, L. W. and Aparicio, R. E. and Geier, E. G. and Ramos, E. M. and Wang, Q. and Karydas, A. and Miller, Z. A. and others},
title = {{Rare TREM2 variants associated with Alzheimer's disease display reduced cell surface expression}},
journal = {Acta neuropathologica communications},
year = {2016},
doi = {10.1186/s40478-016-0367-7},
pmid = {27589997},
url = {https://doi.org/10.1186/s40478-016-0367-7}
}
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