ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2018
Human ApoE Isoforms Differentially Modulate Brain Glucose and Ketone Body Metabolism: Implications for Alzheimer's Disease Risk Reduction and Early Intervention.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
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Who cites it
122 citing papers in PubMed, 2 syntheses or guidelines pooled it, 187 citations in OpenAlex.
- Ketogenic interventions in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease: A systematic review and critical appraisal.Frontiers in neurology · 2023Pooled it
- APOE4 is associated with cognitive and pathological heterogeneity in patients with Alzheimer's disease: a systematic review.Alzheimer's research & therapy · 2020Pooled it
- Apolipoprotein E ε4 and type 2 diabetes cooperatively accelerate amyloid beta and tau neurodegeneration.European journal of nuclear medicine and molecular imaging · 2026Article
- Engineering Nanoplatforms for Alzheimer's Disease Detection via Biomolecular Corona Proteomic and Lipidomic Profiling.Advanced healthcare materials · 2026Article
- Kinetic Lipidomics: QuantifyingbioRxiv : the preprint server for biology · 2026Article
- Review
- The Variant T Allele ofBiomolecules · 2026Article
- APOE4 Accelerates Menopause-Associated Brain Metabolic Shift and Disrupts Bioenergetic Adaptation.bioRxiv : the preprint server for biology · 2026Article
- Dietary Bioactives in Alzheimer's Disease: A Critical Appraisal of Clinical Trials and Future Nutritional Strategies.Nutrients · 2026Review
- APOE-ε4 genotype and western diet synergistically aggravate synaptic dysfunction in Alzheimer's disease via D-serine disruption.Alzheimer's research & therapy · 2026Article
- Discrimination of Bipolar Disorder and Schizophrenia Patients Based on LC-HRMS Lipidomics.Metabolites · 2026Article
- APOE4 accelerates menopause-associated brain metabolic shift and disrupts bioenergetic adaptation.Frontiers in aging neuroscience · 2026Article
- Lysophosphatidylcholines are associated with amyloidosis in early stages of Alzheimer's disease.Nature aging · 2026Article
- Human Apolipoprotein E ε4 Allele Modulates Energy Substrate Availability, Seizure Burden, Mortality and Hippocampal Injury, Cell Death, and Inflammation after Neonatal Hypoxic-Ischemic Brain Injury.Developmental neuroscience · 2026Article
- Hexokinase as a Central Hub in Neurodegeneration: From Metabolic Dysfunction to Therapeutic Innovation.Aging and disease · 2025Review
- Article
- Acute high glucose exposure impairs synaptosomal vesicle release activity.Brain research · 2025Article
- APOE genotype influences on the brain metabolome of aging mice - role for mitochondrial energetics in mechanisms of resilience in APOE2 genotype.Molecular neurodegeneration · 2025Article
- Ketogenic Diet Modulates Gut Microbiota-Brain Metabolite Axis in a Sex- and Genotype-Specific Manner in APOE4 Mice.Journal of neurochemistry · 2025Article
- Fueling the brain - the role of apolipoprotein E in brain energy metabolism and its implications for Alzheimer's disease.Translational psychiatry · 2025Review
62 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
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Humans possess three genetic isoforms of apolipoprotein E (ApoE)-ApoE2, ApoE3, and ApoE4-that confer differential risk for Alzheimer's disease (AD); however, the underlying mechanisms are poorly understood. This study sought to investigate the impact of human ApoE isoforms on brain energy metabolism, an area significantly perturbed in preclinical AD. A TaqMan custom array was performed to examine the expression of a total of 43 genes involved in glucose and ketone body transport and metabolism, focusing on pathways leading to the generation of acetyl-CoA, in human ApoE gene-targeted replacement female mice. Consistent with our previous findings, brains expressing ApoE2 exhibited the most robust profile, whereas brains expressing ApoE4 displayed the most deficient profile on the uptake and metabolism of glucose, the primary fuel for the brain. Specifically, the three ApoE brains differed significantly in facilitated glucose transporters, which mediate the entry of glucose into neurons, and hexokinases, which act as the "gateway enzyme" in glucose metabolism. Interestingly, on the uptake and metabolism of ketone bodies, the secondary energy source for the brain, ApoE2 and ApoE4 brains showed a similar level of robustness, whereas ApoE3 brains presented a relatively deficient profile. Further, ingenuity pathway analysis indicated that the PPAR-γ/PGC-1α signaling pathway could be activated in the ApoE2 brain and inhibited in the ApoE4 brain. Notably, PGC-1α overexpression ameliorated ApoE4-induced deficits in glycolysis and mitochondrial respiration. Overall, our data provide additional evidence that human ApoE isoforms differentially modulate brain bioenergetic metabolism, which could serve as a potential mechanism contributing to their discrete risk impact in AD.
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What OpenQuestion holds
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.