ArticleMolecular neurodegeneration2021
APOΕ4 lowers energy expenditure in females and impairs glucose oxidation by increasing flux through aerobic glycolysis.
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 66 papers, 2 of them syntheses that pooled it.
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Who cites it
66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Pooled it
- Pooled it
- Review
- Ontological Analysis of Brain Proteostasis Highlights the Sex-Dependent Trajectory of ApoE Isoform-Specific Regulation.bioRxiv : the preprint server for biology · 2026Article
- Sex differences in brain glucose metabolism and Alzheimer's disease risk and progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Review
- The physiological effects of APOE genotype in healthy young/middle-aged individuals.Biological reviews of the Cambridge Philosophical Society · 2026Article
- Glycolysis: The Bridge Between Cellular Interaction and Alzheimer's Disease.Biomolecules · 2026Review
- Genome-scale metabolic modeling uncovers cell-type specific signatures associated with APOE variants.iScience · 2026Article
- Establishment and validation of an Alzheimer's disease diagnostic model on the basis of exhaled volatile organic compound characteristics.Translational psychiatry · 2026Article
- Article
- APOE4 Accelerates Menopause-Associated Brain Metabolic Shift and Disrupts Bioenergetic Adaptation.bioRxiv : the preprint server for biology · 2026Article
- Article
- APOE-ε4 genotype and western diet synergistically aggravate synaptic dysfunction in Alzheimer's disease via D-serine disruption.Alzheimer's research & therapy · 2026Article
- APOE4 drives maladaptive heterogeneity and immunometabolic responses of astrocytes.Journal of neuroinflammation · 2026Article
- APOE4 accelerates menopause-associated brain metabolic shift and disrupts bioenergetic adaptation.Frontiers in aging neuroscience · 2026Article
- Beyond Fuel: Exercise-Induced Lactate as a Metabolic-Epigenetic Regulator in Central Nervous System Health and Disease.Biomolecules · 2025Review
- Interaction of sortilin with apolipoprotein E3 enables neurons to use long-chain fatty acids as alternative metabolic fuel.Nature metabolism · 2025Article
- Fueling the brain - the role of apolipoprotein E in brain energy metabolism and its implications for Alzheimer's disease.Translational psychiatry · 2025Review
- APOE4 reshapes the lipid droplet proteome and modulates microglial inflammatory responses.Neurobiology of disease · 2025Article
6 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
22 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.
methodsHere, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.
resultsSingle-cell analysis of brain tissue from mice expressing human APOE revealed E4-associated decreases in genes related to oxidative phosphorylation, particularly in astrocytes. This shift was confirmed on a metabolic level with isotopic tracing of
conclusionsTogether, these results suggest astrocyte, brain and system-level metabolic reprogramming in the presence of APOE4, a 'Warburg like' endophenotype that is observable in young females decades prior to clinically manifest AD.
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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.