ArticleScientific reports2017
Apolipoprotein E4 and Insulin Resistance Interact to Impair Cognition and Alter the Epigenome and Metabolome.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 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
- Diabetes-Associated Cognitive Dysfunction: Pathophysiology, Molecular Mechanisms, and Emerging Therapeutic Strategies.ACS pharmacology & translational science · 2026Review
- Apolipoprotein E ε4 and type 2 diabetes cooperatively accelerate amyloid beta and tau neurodegeneration.European journal of nuclear medicine and molecular imaging · 2026Article
- Trajectory-Oriented Brain Vulnerability Framework for Cognitive Decline in Type 2 Diabetes.International journal of molecular sciences · 2026Review
- Article
- High-fat Western diet induces retinal and metabolic alterations in APOE3 and APOE4 knock-in mice.Scientific reports · 2026Article
- Research Progress on Pathology, Molecular Mechanisms, and Intervention Strategies of Cognitive Dysfunction Associated with Type 2 Diabetes.International journal of general medicine · 2026Review
- 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
- Pathological mechanisms and treatment progression of Alzheimer's disease.European journal of medical research · 2025Review
- Proteomic and metabolic profiling revealsbioRxiv : the preprint server for biology · 2025Article
- Protection against APOE4-associated phenotypes with the longevity-promoting intervention 17α-estradiol in middle-aged male mice.Communications medicine · 2025Article
- Risk Factors, Pathological Changes, and Potential Treatment of Diabetes-Associated Cognitive Dysfunction.Journal of diabetes · 2025Review
- Permutations of cerebrovascular pathologies in older adults with and without diabetes.Cerebral circulation - cognition and behavior · 2025Article
- Nonlipogenic ABCA1 Inducers (NLAI) for Alzheimer's Disease Validated in a Mouse Model Expressing HumanJournal of medicinal chemistry · 2024Article
- Insights into the roles of Apolipoprotein E in adipocyte biology and obesity.International journal of obesity (2005) · 2024Review
- Effects of a high-fat diet on cognition and brain distribution of intranasal insulin in E3 and E4 male and female mice.Scientific reports · 2024Article
- State of the Science on Brain Insulin Resistance and Cognitive Decline Due to Alzheimer's Disease.Aging and disease · 2024Review
- Obesity affects brain cortex gene expression in an APOE genotype and sex dependent manner.International journal of obesity (2005) · 2024Article
- Literary Identification of Differentially Hydroxymethylated DNA Regions for Type 2 Diabetes Mellitus: A Scoping Minireview.International journal of environmental research and public health · 2024Article
8 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
5 authors at 2 institutions in 1 country.
Funding
Abstract
Apolipoprotein E4 (E4) and type 2 diabetes are major risk factors for cognitive decline and late onset Alzheimer's disease (AD). E4-associated phenotypes and insulin resistance (IR) share several features and appear to interact in driving cognitive dysfunction. However, shared mechanisms that could explain their overlapping pathophysiology have yet to be found. We hypothesized that, compared to E3 mice, E4 mice would be more susceptible to the harmful cognitive effects of high fat diet (HFD)-induced IR due to apoE isoform-specific differences in brain metabolism. While both E3 and E4 mice fed HFD displayed impairments in peripheral metabolism and cognition, deficits in hippocampal-dependent spatial learning and memory were exaggerated in E4 mice. Combining genome-wide measures of DNA hydroxymethylation with comprehensive untargeted metabolomics, we identified novel alterations in purine metabolism, glutamate metabolism, and the pentose phosphate pathway. Finally, in E4 mice, the metabolic and cognitive deficiencies caused by HFD were rescued by switching to a low fat diet for one month, suggesting a functional role was associated with reversal of the same metabolic pathways described above. These results suggest a susceptibility of E4 carriers to metabolic impairments brought on by IR, and may guide development of novel therapies for cognitive decline and dementia.
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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.