ArticleScientific reports2014
Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- APOE4 is associated with cognitive and pathological heterogeneity in patients with Alzheimer's disease: a systematic review.Alzheimer's research & therapy · 2020Pooled it
- Review
- High-fat Western diet induces retinal and metabolic alterations in APOE3 and APOE4 knock-in mice.Scientific reports · 2026Article
- Fueling the brain - the role of apolipoprotein E in brain energy metabolism and its implications for Alzheimer's disease.Translational psychiatry · 2025Review
- Long-term Dietary Fat Intervention Affects Retinal Health in APOE Mice.bioRxiv : the preprint server for biology · 2025Article
- The multifaceted roles of apolipoprotein E4 in Alzheimer's disease pathology and potential therapeutic strategies.Cell death discovery · 2025Review
- Modulation of the cognitive impairment associated with Alzheimer's disease by valproic acid: possible drug repurposing.Inflammopharmacology · 2025Article
- Brain uptake pharmacokinetics of albiglutide, dulaglutide, tirzepatide, and DA5-CH in the search for new treatments of Alzheimer's and Parkinson's diseases.Tissue barriers · 2024Article
- Multiple Roles of Apolipoprotein E4 in Oxidative Lipid Metabolism and Ferroptosis During the Pathogenesis of Alzheimer's Disease.Journal of molecular neuroscience : MN · 2024Review
- Why Is Iron Deficiency/Anemia Linked to Alzheimer's Disease and Its Comorbidities, and How Is It Prevented?Biomedicines · 2023Review
- Predictive link between systemic metabolism and cytokine signatures in the brain of apolipoprotein E ε4 mice.Neurobiology of aging · 2023Article
- Brain integrity is altered by hepatic APOE ε4 in humanized-liver mice.Molecular psychiatry · 2022Article
- The Insulin Receptor: An Important Target for the Development of Novel Medicines and Pesticides.International journal of molecular sciences · 2022Review
- Defects of Nutrient Signaling and Autophagy in Neurodegeneration.Frontiers in cell and developmental biology · 2022Review
- Astrocytes as Key Regulators of Brain Energy Metabolism: New Therapeutic Perspectives.Frontiers in physiology · 2021Review
- APOE4 is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in Aged APOE Mice.Scientific reports · 2020Article
- Central and Peripheral Mechanisms in ApoE4-Driven Diabetic Pathology.International journal of molecular sciences · 2020Article
- ApoE4: an emerging therapeutic target for Alzheimer's disease.BMC medicine · 2019Review
- A context-based ABC model for literature-based discovery.PloS one · 2019Article
- [Long-term high-fat diet inhibits hippocampal expression of insulin receptor substrates and accelerates cognitive deterioration in obese rats].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Human ApoE4 accelerates memory decline in ageing and in Alzheimer's disease. Although intranasal insulin can improve cognition, this has little effect in ApoE4 subjects. To understand this ApoE genotype-dependent effect, we examined brain insulin signaling in huApoE3 and huApoE4 targeted replacement (TR) mice. At 32 weeks, lower insulin receptor substrate 1 (IRS1) at S636/639 and Akt phosphorylation at T308 were detected in fasting huApoE4 TR mice as compared to fasting huApoE3 TR mice. These changes in fasting huApoE4 TR mice were linked to lower brain glucose content and have no effect on plasma glucose level. However, at 72 weeks of age, these early changes were accompanied by reduction in IRS2 expression, IRS1 phosphorylation at Y608, Akt phosphorylation at S473, and MAPK (p38 and p44/42) activation in the fasting huApoE4 TR mice. The lower brain glucose was significantly associated with higher brain insulin in the aged huApoE4 TR mice. These results show that ApoE4 reduces brain insulin signaling and glucose level leading to higher insulin content.
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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.