Home › Research › Lewy body dementia
TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis
Kleinberger G, Yamanishi Y, Suárez-Calvet M, Czirr E, Lohmann E, Cuyvers E, Struyfs H, Pettkus N et al.. Science translational medicine, 2014-07-01
Topic: Brain proteins, microglia and lab models
Genetic variants in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to Nasu-Hakola disease, Alzheimer's disease (AD), Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and FTD-like syndrome without bone involvement. TREM2 is an innate immune receptor preferentially expressed by microglia and is involved in inflammation and phagocytosis. Whether and how TREM2 missense mutations affect TREM2 function is unclear. We report that missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells. As a consequence of reduced shedding, TREM2 is virtually absent in the cerebrospinal fluid (CSF) and plasma of a patient with FTD-like syndrome. A decrease in soluble TREM2 was also observed in the CSF of patients with AD and FTD, further suggesting that reduced TREM2 function may contribute to increased risk for two neurodegenerative disorders.
Key findings
- We report that missense mutations associated with FTD and FTD-like syndrome reduce TREM2 maturation, abolish shedding by ADAM proteases, and impair the phagocytic activity of TREM2-expressing cells.
- A decrease in soluble TREM2 was also observed in the CSF of patients with AD and FTD, further suggesting that reduced TREM2 function may contribute to increased risk for two neurodegenerative disorders.
Why it matters
This laboratory work found that certain TREM2 mutations reduce the receptor's maturation, stop its shedding by ADAM proteases, and impair the phagocytic activity of cells expressing it. Lower soluble TREM2 was also seen in the cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia, suggesting reduced TREM2 function may contribute to increased risk for these disorders.
Study details
- Evidence strengthLow
How this study scored 58/100
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 (Science translational medicine) |
| Journal's citation record | 3 / 4 | Science Translational Medicine: journal h-index 365 (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 | 2014 — 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 | 6 / 7 | Cited 798 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 57.0 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 5 / 6 | Cited 23.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 5 / 6 | Cited by 177 other studies in this library |
| Still being cited | 3 / 4 | Cited 176 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Christian Haass: h-index 139 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Stanford University: institution h-index 2,684 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 23 institution(s) in 7 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24990881) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 58 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription OpenAlex found no free copy of the full text (checked 6 Feb 1020), so the publisher may charge for it. The PubMed abstract is free.
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
Kleinberger, G., Yamanishi, Y., Suárez-Calvet, M., Czirr, E., Lohmann, E., Cuyvers, E., et al. (2014). TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Science translational medicine. https://doi.org/10.1126/scitranslmed.3009093
Vancouver
Kleinberger G, Yamanishi Y, Suárez-Calvet M, Czirr E, Lohmann E, Cuyvers E, et al. TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Science translational medicine. 2014. doi:10.1126/scitranslmed.3009093. PMID: 24990881.
BibTeX
@article{kleinberger2014-24990881,
author = {Kleinberger, G. and Yamanishi, Y. and Suárez-Calvet, M. and Czirr, E. and Lohmann, E. and Cuyvers, E. and Struyfs, H. and Pettkus, N. and others},
title = {{TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis}},
journal = {Science translational medicine},
year = {2014},
doi = {10.1126/scitranslmed.3009093},
pmid = {24990881},
url = {https://doi.org/10.1126/scitranslmed.3009093}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 25.
Later studies that cite this one
177 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Lewy body dementia
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.