Evidence map›Paper›PMID 31907987›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020

A locked immunometabolic switch underlies TREM2 R47H loss of function in human iPSC-derived microglia.

Thomas M Piers, Katharina Cosker, Anna Mallach, Gabriel Thomas Johnson, Rita Guerreiro, John Hardy, Jennifer M Pocock

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

86 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.

  1. Pooled it
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  6. Abi3Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  7. Review
  8. Article
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  10. Article
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  14. Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025
    Review
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  17. Article
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  20. Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025
    Review

26 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Thomas M PiersDepartment of Neuroinflammation, University College London Queen Square Institute of Neurology, London, UK.
Katharina CoskerDepartment of Neuroinflammation, University College London Queen Square Institute of Neurology, London, UK.
Anna MallachDepartment of Neuroinflammation, University College London Queen Square Institute of Neurology, London, UK.
Gabriel Thomas JohnsonDepartment of Neuroinflammation, University College London Queen Square Institute of Neurology, London, UK.
Rita GuerreiroCenter for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI, USA.
John HardyDepartment of Neurodegenerative Diseases, University College London Queen Square Institute of Neurology, London, UK.
Jennifer M PocockDepartment of Neuroinflammation, University College London Queen Square Institute of Neurology, London, UK.
National Hospital for Neurology and Neurosurgery · GBUniversity College London · GBQueen Mary University of London · GBVan Andel Institute · US

Funding

Biotechnology and Biological Sciences Research Council BB/M009513/1Medical Research Council G0701075Medical Research Council G0901254Medical Research Council MR/L501542/1Medical Research Council MR/M02492X/1Medical Research Council MR/N026004/1Parkinson's UK G-0907
6 · The paper itself

Abstract

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. 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. We determined that dysregulated PPARγ/p38MAPK signaling underlies the observed phenotypic deficits in TREM2 variants and that activation of these pathways can ameliorate the metabolic deficit in these cells and consequently rescue critical microglial cellular function such as β-Amyloid phagocytosis. These findings have ramifications for microglial focussed-treatments in AD.

Indexed as

Alzheimer DiseaseInduced Pluripotent Stem CellsLoss of Function MutationMembrane GlycoproteinsMicrogliaReceptors, ImmunologicCell DifferentiationCell LineHumansMembrane GlycoproteinsReceptors, ImmunologicTREM2 protein, humanAlzheimer's diseaseglycolysismetabolismmicroglia

Identifiers

PMID31907987
PMCPMC7027848
OpenAlexW2997545733

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.