ArticleNeuron2017
Apolipoprotein E4 Impairs Neuronal Insulin Signaling by Trapping Insulin Receptor in the Endosomes.
Article in Neuron, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
189 citing papers in PubMed, 2 syntheses or guidelines pooled it, 279 citations in OpenAlex.
- To Keto or Not to Keto? A Systematic Review of Randomized Controlled Trials Assessing the Effects of Ketogenic Therapy on Alzheimer Disease.Advances in nutrition (Bethesda, Md.) · 2020Pooled it
- APOE4 is associated with cognitive and pathological heterogeneity in patients with Alzheimer's disease: a systematic review.Alzheimer's research & therapy · 2020Pooled it
- Diabetic cerebral microvascular disorder: from key pathologies to targeted interventions.Annals of medicine · 2026Review
- Insulin mimetics and non-canonical insulin receptor signaling: mechanisms and disease relevance.Experimental & molecular medicine · 2026Review
- Apolipoprotein E ε4 and type 2 diabetes cooperatively accelerate amyloid beta and tau neurodegeneration.European journal of nuclear medicine and molecular imaging · 2026Article
- The Crosstalk Between Diabetes and Alzheimer's Disease: A Molecular Perspective.Basic & clinical pharmacology & toxicology · 2026Review
- Shared genetic and molecular architecture between insulin resistance and cognitive performance.medRxiv : the preprint server for health sciences · 2026Article
- The Interaction Between Insulin Resistance and Neuroinflammation in the Brain and Its Impact on Diabetic Encephalopathy.Biology · 2026Review
- Review
- Connecting the Dots: Neurobiological Interplay Between Type 2 Diabetes and Alzheimer's Disease.International journal of molecular sciences · 2026Review
- APOE4 Accelerates Menopause-Associated Brain Metabolic Shift and Disrupts Bioenergetic Adaptation.bioRxiv : the preprint server for biology · 2026Article
- Structural Change of ApoE-Lipid Nanoparticles Alters Receptor-Mediated Endocytosis and Induces Endosomal Disruption.Journal of the American Chemical Society · 2026Article
- Examining APOE ε4 and Longitudinal Vascular Brain Injury: The Strong Heart Study.Neurology open access · 2026Article
- Metabolic Dysfunction in Alzheimer's Disease: Brain Glucose Hypometabolism as an Early Precursor to Amyloid and Tau Pathology.Journal of clinical medicine · 2026Review
- Article
- Metformin provides superior neuroprotective potential compared to semaglutide in preventing diabetes-associated Alzheimer's disease via dual actions.Communications medicine · 2026Article
- High-fat Western diet induces retinal and metabolic alterations in APOE3 and APOE4 knock-in mice.Scientific reports · 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
- Insulin resistance (TyG index) and body mass index as metabolic biomarker combined with ApoE genotype to diagnose Alzheimer's disease.Frontiers in aging neuroscience · 2026Article
- Targeting the astrocytic metabolic cascade in Alzheimer's disease: mechanisms, challenges and opportunities.Frontiers in aging neuroscience · 2026Review
129 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
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Diabetes and impaired brain insulin signaling are linked to the pathogenesis of Alzheimer's disease (AD). The association between diabetes and AD-associated amyloid pathology is stronger among carriers of the apolipoprotein E (APOE) ε4 gene allele, the strongest genetic risk factor for late-onset AD. Here we report that apoE4 impairs neuronal insulin signaling in human apoE-targeted replacement (TR) mice in an age-dependent manner. High-fat diet (HFD) accelerates these effects in apoE4-TR mice at middle age. In primary neurons, apoE4 interacts with insulin receptor and impairs its trafficking by trapping it in the endosomes, leading to impaired insulin signaling and insulin-stimulated mitochondrial respiration and glycolysis. In aging brains, the increased apoE4 aggregation and compromised endosomal function further exacerbate the inhibitory effects of apoE4 on insulin signaling and related functions. Together, our study provides novel mechanistic insights into the pathogenic mechanisms of apoE4 and insulin resistance in AD.
Indexed as
Identifiers
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.