Evidence map›Paper›PMID 35931030›Full record

ArticleCell stem cell2022

Lipid accumulation induced by APOE4 impairs microglial surveillance of neuronal-network activity.

Matheus B Victor, Noelle Leary, Xochitl Luna, Hiruy S Meharena, Aine Ni Scannail, P Lorenzo Bozzelli, George Samaan, Mitchell H Murdock, Djuna von Maydell, Audrey H Effenberger and 6 more

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

Article in Cell stem cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 214 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
214citing papers in PubMed, 2 pooled it
22.1field-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

214 citing papers in PubMed, 2 syntheses or guidelines pooled it, 261 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. miR-214-3p and NCKAP1: A microglial functional dimension of Alzheimer's progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  5. Article
  6. ApoE lipidation state directs immunometabolic reprogramming of human microglia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  7. Human iPSC models revealResearch square · 2026
    Article
  8. Neurons run on fat.npj metabolic health and disease · 2026
    Article
  9. Article
  10. Aberrant phase separation from a rare ABI3 mutation drives microglial dysfunction and Alzheimer's risk.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  11. Review
  12. Article
  13. Review
  14. Article
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  16. Article
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154 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 1 institution in 1 country.

Matheus B VictorPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Noelle LearyPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Xochitl LunaPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Hiruy S MeharenaPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Aine Ni ScannailPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
P Lorenzo BozzelliPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
George SamaanPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Mitchell H MurdockPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Djuna von MaydellPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Audrey H EffenbergerPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Oyku CeritPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Hsin-Lan WenPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Liwang LiuPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Gwyneth WelchPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Maeve BonnerPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Li-Huei TsaiPicower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: lhtsai@mit.edu.
Massachusetts Institute of Technology · US

Funding

Epigenomic, transcriptional and cellular dissection of Alzheimer's variantsR01AG058002 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HYMAN, BRADLEY T., JAENISCH, RUDOLF · 2017 to 2021
$7.9M
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 R01 AG058002NIA NIH HHS RF1 AG062377
6 · The paper itself

Abstract

Apolipoprotein E4 (APOE4) is the greatest known genetic risk factor for developing sporadic Alzheimer's disease. How the interaction of APOE4 microglia with neurons differs from microglia expressing the disease-neutral APOE3 allele remains unknown. Here, we employ CRISPR-edited induced pluripotent stem cells (iPSCs) to dissect the impact of APOE4 in neuron-microglia communication. Our results reveal that APOE4 induces a lipid-accumulated state that renders microglia weakly responsive to neuronal activity. By examining the transcriptional signatures of APOE3 versus APOE4 microglia in response to neuronal conditioned media, we established that neuronal cues differentially induce a lipogenic program in APOE4 microglia that exacerbates pro-inflammatory signals. Through decreased uptake of extracellular fatty acids and lipoproteins, we identified that APOE4 microglia disrupts the coordinated activity of neuronal ensembles. These findings suggest that abnormal neuronal network-level disturbances observed in Alzheimer's disease patients harboring APOE4 may in part be triggered by impairment in lipid homeostasis in non-neuronal cells.

Indexed as

Alzheimer DiseaseApolipoprotein E4Apolipoprotein E3HumansMicrogliaNeuronsApolipoprotein E3Apolipoprotein E4Alzheimer’s risk variantAPOEcalcium dynamicsforebrain spheroidsGIRKslipid dropletmicroglianetwork-activitystem cells

Identifiers

PMID35931030
PMCPMC9623845
OpenAlexW4289793560

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.