Evidence map›Paper›PMID 37969043›Full record

ArticleGlia2024

iPSC-derived microglia carrying the TREM2 R47H/+ mutation are proinflammatory and promote synapse loss.

Jay Penney, William T Ralvenius, Anjanet Loon, Oyku Cerit, Vishnu Dileep, Blerta Milo, Ping-Chieh Pao, Hannah Woolf, Li-Huei Tsai

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

Article in Glia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Pooled it
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  13. Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026
    Review
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  17. Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025
    Review
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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

9 authors at 3 institutions in 2 countries.

Jay PenneyPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.ORCID 0000-0001-5607-113X
William T RalveniusPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Anjanet LoonPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Oyku CeritPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Vishnu DileepPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Blerta MiloPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Ping-Chieh PaoPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Hannah WoolfPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Li-Huei TsaiPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Institute of Cognitive and Brain Sciences · USBroad Institute · USUniversity of Prince Edward Island · CA

Funding

Demystifying Microglia in Aging and Alzheimer's DiseaseRF1AG054321 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI DE JAGER, PHILIP L, LEVIN, JOSHUA ZVI · 2016 to 2016
$4.0M
Dissection of endosomal trafficking mechanisms in Alzheimer's DiseaseRF1AG062377 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI TSAI, LI-HUEI · 2018 to 2018
$3.6M
NIA NIH HHS RF1 AG054321NIA NIH HHS RF1 AG062377
6 · The paper itself

Abstract

Genetic findings have highlighted key roles for microglia in the pathology of neurodegenerative conditions such as Alzheimer's disease (AD). A number of mutations in the microglial protein triggering receptor expressed on myeloid cells 2 (TREM2) have been associated with increased risk for developing AD, most notably the R47H/+ substitution. We employed gene editing and stem cell models to gain insight into the effects of the TREM2 R47H/+ mutation on human-induced pluripotent stem cell-derived microglia. We found transcriptional changes affecting numerous cellular processes, with R47H/+ cells exhibiting a proinflammatory gene expression signature. TREM2 R47H/+ also caused impairments in microglial movement and the uptake of multiple substrates, as well as rendering microglia hyperresponsive to inflammatory stimuli. We developed an in vitro laser-induced injury model in neuron-microglia cocultures, finding an impaired injury response by TREM2 R47H/+ microglia. Furthermore, mouse brains transplanted with TREM2 R47H/+ microglia exhibited reduced synaptic density, with upregulation of multiple complement cascade components in TREM2 R47H/+ microglia suggesting inappropriate synaptic pruning as one potential mechanism. These findings identify a number of potentially detrimental effects of the TREM2 R47H/+ mutation on microglial gene expression and function likely to underlie its association with AD.

Indexed as

Alzheimer DiseaseInduced Pluripotent Stem CellsAnimalsBrainHumansMembrane GlycoproteinsMiceMicrogliaMutationReceptors, ImmunologicSynapsesMembrane GlycoproteinsReceptors, ImmunologicTREM2 protein, humanAlzheimer's diseaseinduced pluripotent stem cellsinflammationmicroglianeurodegenerationtriggering receptor expressed on myeloid cells 2 (TREM2)

Identifiers

PMID37969043
PMCPMC10904109
OpenAlexW4388727494

What OpenQuestion holds

Textmetadata
LicenceTDM
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.