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A locked immunometabolic switch underlies TREM2 R47H loss of function in human iPSC-derived microglia
Piers TM, Cosker K, Mallach A, Johnson GT, Guerreiro R, Hardy J, Pocock JM.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019-12-23
Topic: Brain proteins, microglia and lab models
Loss-of-function genetic variants of triggering receptor expressed on myeloid cells 2 (TREM2) are linked with an enhanced risk of developing dementias. Microglia, the resident immune cell of the brain, express TREM2, and microglial responses are implicated in dementia pathways. In a normal surveillance state, microglia use oxidative phosphorylation for their energy supply, but rely on the ability to undergo a metabolic switch to glycolysis to allow them to perform rapid plastic responses.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Piers, T. M., Cosker, K., Mallach, A., Johnson, G. T., Guerreiro, R., Hardy, J., et al. (2020). A locked immunometabolic switch underlies TREM2 R47H loss of function in human iPSC-derived microglia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. https://doi.org/10.1096/fj.201902447r
Vancouver
Piers TM, Cosker K, Mallach A, Johnson GT, Guerreiro R, Hardy J, et al. A locked immunometabolic switch underlies TREM2 R47H loss of function in human iPSC-derived microglia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2020. doi:10.1096/fj.201902447r. PMID: 31907987.
BibTeX
@article{piers2020-31907987,
author = {Piers, T. M. and Cosker, K. and Mallach, A. and Johnson, G. T. and Guerreiro, R. and Hardy, J. and Pocock, J. M.},
title = {{A locked immunometabolic switch underlies TREM2 R47H loss of function in human iPSC-derived microglia}},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
year = {2020},
doi = {10.1096/fj.201902447r},
pmid = {31907987},
url = {https://doi.org/10.1096/fj.201902447r}
}
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Microglia, the resident immune cell of the brain, express TREM2, and microglial responses are implicated in dementia pathways.
- In a normal surveillance state, microglia use oxidative phosphorylation for their energy supply, but rely on the ability to undergo a metabolic switch to glycolysis to allow them to perform rapid plastic responses.
- We investigated the role of TREM2 on the microglial metabolic function in human patient iPSC-derived microglia expressing loss of function variants in TREM2.
- We show that these TREM2 variant iPSC-microglia, including the Alzheimer's disease R47H risk variant, exhibit significant metabolic deficits including a reduced mitochondrial respiratory capacity and an inability to perform a glycolytic immunometabolic switch.
Why it matters
Using human iPSC-derived microglia, this study found that loss-of-function TREM2 variants lock a metabolic switch, which may impair microglial responses relevant to dementia. It is cell-based laboratory work and does not demonstrate a treatment.
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Study details
- Evidence strengthLow
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (FASEB journal : official publication of the Federation of American Societies for Experimental Biology) |
| Journal's citation record | 3 / 4 | The FASEB Journal: journal h-index 401 (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 | Laboratory or animal study (title names “ipsc”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 134 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.8 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 3 / 6 | Cited 5.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 16 other studies in this library |
| Still being cited | 3 / 4 | Cited 55 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Jennifer M. Pocock: h-index 44 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31907987) |
| Free to read | 2 / 2 | Free to read |
| Total | 49 / 100 | — |
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