ArticleCell reports2023
APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
136 citing papers in PubMed, 2 syntheses or guidelines pooled it, 180 citations in OpenAlex.
- Neurological Manifestations of SARS-CoV-2.Viruses · 2025Pooled it
- The role of APOE ε4 in modulating the relationship between non-genetic risk factors and dementia: a system review and meta-analysis.Journal of neurology · 2025Pooled it
- Failure of Neuroinflammatory Resolution in Brain Aging: Molecular Mechanisms and an Integrative Framework of Microglial Inflammometabolic Locking.Molecular neurobiology · 2026Review
- Spatiotemporal heterogeneity and dynamic evolution of microglial glucose metabolic reprogramming in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- ABCC9/SUR2 has a Complex Expression Pattern in Human Brain Gliovascular Unit Cells, Including Astrocytes.Journal of molecular neuroscience : MN · 2026Article
- A metabolic perspective on microglia in Alzheimer's disease.Neural regeneration research · 2026Article
- APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics.Nature communications · 2026Article
- Review
- Fat on Fire: Disrupted Microglial Lipid Metabolism as a Driver of Anesthetic Neurotoxicity.Neuroscience bulletin · 2026Review
- Metabolic Reprogramming of Brain Microglia: Implications for Aging and Aging-Associated Neurodegenerative Diseases.Aging cell · 2026Review
- Review
- CRM-1 Aggravates Stroke Injury by Promoting BANF1-Mediated Unfolded Protein Response Through Inducing Nuclear Export of ALKBH5.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- SPRY1 suppresses microglial fatty acid oxidation by retaining FATP3 on the endoplasmic reticulum in Alzheimer's disease.Journal of neuroinflammation · 2026Article
- Pharmacological Targeting of Peroxisome Proliferator-activated Receptors for Prevention of Radiation-induced Cognitive Decline.Annals of neurosciences · 2026Review
- Article
- Article
- Targeting the FOXO4-p53 axis by retro-inverso peptide senolytic agents: a pharmacological strategy to mitigate brain aging and cognitive decline.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Anti-amyloid immunotherapy drives APOE4 specific increases in glial reactivity, perivascular immune activation, and ARIA-like events.bioRxiv : the preprint server for biology · 2026Article
- Plasma GDF15 affects long-term dementia risk and alters neuroimmune signaling.Science advances · 2026Article
- APOE4 Drives Uniquely Dysfunctional Human Microglial States in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
76 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
The E4 allele of Apolipoprotein E (APOE) is associated with both metabolic dysfunction and a heightened pro-inflammatory response: two findings that may be intrinsically linked through the concept of immunometabolism. Here, we combined bulk, single-cell, and spatial transcriptomics with cell-specific and spatially resolved metabolic analyses in mice expressing human APOE to systematically address the role of APOE across age, neuroinflammation, and AD pathology. RNA sequencing (RNA-seq) highlighted immunometabolic changes across the APOE4 glial transcriptome, specifically in subsets of metabolically distinct microglia enriched in the E4 brain during aging or following an inflammatory challenge. E4 microglia display increased Hif1α expression and a disrupted tricarboxylic acid (TCA) cycle and are inherently pro-glycolytic, while spatial transcriptomics and mass spectrometry imaging highlight an E4-specific response to amyloid that is characterized by widespread alterations in lipid metabolism. Taken together, our findings emphasize a central role for APOE in regulating microglial immunometabolism and provide valuable, interactive resources for discovery and validation research.
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Registered trials
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.