Evidence map›Paper›PMID 34301296›Full record

ArticleMolecular neurodegeneration2021

Plaque-associated human microglia accumulate lipid droplets in a chimeric model of Alzheimer's disease.

Christel Claes, Emma Pascal Danhash, Jonathan Hasselmann, Jean Paul Chadarevian, Sepideh Kiani Shabestari, Whitney E England, Tau En Lim, Jorge Luis Silva Hidalgo, Robert C Spitale, Hayk Davtyan and 1 more

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

Article in Molecular neurodegeneration, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed, 1 pooled it
12.0field-weighted citation impact, top 1% 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

134 citing papers in PubMed, 1 synthesis or guideline pooled it, 188 citations in OpenAlex.

  1. Pooled it
  2. Review
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  11. Lipid metabolism, microglia, and stroke.Neural regeneration research · 2026
    Article
  12. Article
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  16. How does type 2 diabetes modify the risk of Alzheimer's disease?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  17. Article
  18. Article
  19. Review
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74 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

11 authors at 1 institution in 1 country.

Christel ClaesDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, 92696, USA. cclaes@uci.edu.ORCID 0000-0002-7765-0445
Emma Pascal DanhashSue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, 92696, USA.
Jonathan HasselmannDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, 92696, USA.
Jean Paul ChadarevianDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, 92696, USA.
Sepideh Kiani ShabestariSue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, CA, 92696, USA.
Whitney E EnglandDepartment of Pharmaceutical Sciences, University of California, Irvine, CA, 92697, USA.
Tau En LimDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, 92696, USA.
Jorge Luis Silva HidalgoDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, 92696, USA.
Robert C SpitaleDepartment of Pharmaceutical Sciences, University of California, Irvine, CA, 92697, USA.
Hayk DavtyanDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, 92696, USA.
Mathew Blurton-JonesDepartment of Neurobiology and Behavior, University of California Irvine, Irvine, CA, 92696, USA. mblurton@uci.edu.ORCID 0000-0002-7770-7157
University of California, Irvine · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
UC Irvine Alzheimer's Disease Research Center Induced Pluripotent Stem Cell CoreP50AG016573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2000 to 2019
$37.0M
The Alzheimer's Disease Research Center at the University of California, IrvineP30AG066519 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Elizabeth Head · 2020 to 2026
$27.9M
Using human iPSC derived microglia and chimeric models to examine the role of PLCG2 in Alzheimers diseaseR01AG061895 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAVTYAN, HAYK · 2018 to 2022
$2.9M
Manipulating DNA repair enzymes to examine the interactions between aging and Alzheimers disease with iPSC-derived microgliaR01AG056303 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK · 2017 to 2021
$1.9M
The role of TREM2 in human microglial function and Alzheimer disease pathogenesisRF1AG048099 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK · 2014 to 2014
$1.9M
PacBio RS Single Molecule, Real-Time (SMRT) DNA SequencerS10OD010794 · OD · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2012 to 2012
$600k
High-Throughput DNA SequencerS10OD021718 · OD · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2016 to 2016
$600k
High Throughput DNA SequencerS10RR025496 · NCRR · UNIVERSITY OF CALIFORNIA-IRVINE · PI SANDMEYER, SUZANNE · 2009 to 2009
$500k
NCI NIH HHS P30 CA062203NCRR NIH HHS S10 RR025496NIA NIH HHS P30 AG066519NIA NIH HHS P50 AG016573NIA NIH HHS R01 AG056303NIA NIH HHS R01 AG061895NIA NIH HHS RF1 AG048099NIH HHS S10 OD010794NIH HHS S10 OD021718
6 · The paper itself

Abstract

backgroundDisease-associated microglia (DAMs), that surround beta-amyloid plaques, represent a transcriptionally-distinct microglial profile in Alzheimer's disease (AD). Activation of DAMs is dependent on triggering receptor expressed on myeloid cells 2 (TREM2) in mouse models and the AD TREM2-R47H risk variant reduces microglial activation and plaque association in human carriers. Interestingly, TREM2 has also been identified as a microglial lipid-sensor, and recent data indicates lipid droplet accumulation in aged microglia, that is in turn associated with a dysfunctional proinflammatory phenotype. However, whether lipid droplets (LDs) are present in human microglia in AD and how the R47H mutation affects this remains unknown.

methodsTo determine the impact of the TREM2 R47H mutation on human microglial function in vivo, we transplanted wild-type and isogenic TREM2-R47H iPSC-derived microglial progenitors into our recently developed chimeric Alzheimer mouse model. At 7 months of age scRNA-seq and histological analyses were performed.

resultsHere we report that the transcriptome of human wild-type TREM2 and isogenic TREM2-R47H DAM xenografted microglia (xMGs), isolated from chimeric AD mice, closely resembles that of human atherosclerotic foam cells. In addition, much like foam cells, plaque-bound xMGs are highly enriched in lipid droplets. Somewhat surprisingly and in contrast to a recent in vitro study, TREM2-R47H mutant xMGs exhibit an overall reduction in the accumulation of lipid droplets in vivo. Notably, TREM2-R47H xMGs also show overall reduced reactivity to plaques, including diminished plaque-proximity, reduced CD9 expression, and lower secretion of plaque-associated APOE.

conclusionsAltogether, these results indicate lipid droplet accumulation occurs in human DAM xMGs in AD, but is reduced in TREM2-R47H DAM xMGs, as it occurs secondary to TREM2-mediated changes in plaque proximity and reactivity.

Indexed as

Membrane GlycoproteinsReceptors, ImmunologicAlzheimer DiseaseAnimalsBrainChimeraDisease Models, AnimalHeterograftsHumansLipid DropletsMiceMicrogliaMembrane GlycoproteinsReceptors, ImmunologicTREM2 protein, humanChimeric Alzheimer miceHuman microgliaLipid dropletsTREM2

Identifiers

PMID34301296
PMCPMC8305935
OpenAlexW3184188306

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Registered trials

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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.