ArticleThe Journal of pathology2011
Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes.
Article in The Journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 271 papers.
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Who cites it
271 citing papers in PubMed, 493 citations in OpenAlex.
- Blood-Brain Glucose Transfer in Alzheimer's disease: Effect of GLP-1 Analog Treatment.Scientific reports · 2017Trial
- Diabetes-Associated Cognitive Impairment: Pathophysiology and Emerging Therapies.Annals of clinical and translational neurology · 2026Review
- Sleeve Gastrectomy Improves Metabolic Health, Cognition, and Alzheimer's Disease Pathology in 3xTG Mice.Aging cell · 2026Article
- Insulin Receptor Isoform Pattern in Aged Normal and Alzheimer's Human Cortex.Journal of neurochemistry · 2026Article
- Sleeve gastrectomy improves metabolic health, cognition, and Alzheimer's Disease pathology in 3xTG mice.bioRxiv : the preprint server for biology · 2026Article
- Complementary neuroprotective effects of semaglutide and papaya in diabetic encephalopathy via antioxidant and insulin-signaling pathways.Scientific reports · 2026Article
- Systems biology of Alzheimer's Disease: a scoping review of key pathways and mechanisms.Molecular neurodegeneration · 2026Article
- Insulin Signaling in Alzheimer's Disease: Association with Brain Insulin Resistance.International journal of molecular sciences · 2026Review
- Mechanisms and therapeutic strategies of ferroptosis in Diabetic-Associated Cognitive Dysfunction: focus on the crosstalk with apoptosis, autophagy, and pyroptosis.Molecular biology reports · 2026Review
- Pharmacological modulation of the PI3K/AKT/GSK3β axis: a new frontier in Alzheimer's disease treatment.Inflammopharmacology · 2026Review
- Antibody-conjugated polymer nanoparticles for brain cancer.Drug delivery and translational research · 2025Review
- The Multi-Dimensional Action Map of Resveratrol Against Alzheimer's Disease: Mechanism Integration and Treatment Strategy Optimization.Nutrients · 2025Review
- Effects of Dietary Vitamin D Levels on Markers Related to Amyloidogenesis and Neuroinflammation in db/db Mice.Nutrients · 2025Article
- Cholinergic neurotransmission in the brain of streptozotocin-induced rat model of sporadic Alzheimer's disease: long-term follow up.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Association of genetic scores related to insulin resistance with neurological outcomes in ancestrally diverse cohorts from the Trans-Omics for Precision Medicine (TOPMed) program.Communications biology · 2025Article
- Age-Related Complement C3 Drives Memory Impairments and Associated Neuropathologies in a Mouse Model.Aging cell · 2025Article
- Repurposing Saroglitazar for neurodegenerative disorders: insight into molecular signalling pathways and neuroprotective modulations.Inflammopharmacology · 2025Review
- Target Validation Studies of PS48, a PDK-1 Allosteric Agonist, for the Treatment of Alzheimer's Disease Phenotype in APP/PS1 Transgenic Mice.International journal of molecular sciences · 2025Article
- Insulin resistance in Alzheimer's disease: signalling mechanisms and therapeutics strategies.Inflammopharmacology · 2025Review
- Pea Peptide Modulates Abnormal Aβ Production in PC12 Cells Induced by Lead Exposure.Plant foods for human nutrition (Dordrecht, Netherlands) · 2025Article
211 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Brain glucose metabolism is impaired in Alzheimer's disease (AD), the most common form of dementia. Type 2 diabetes mellitus (T2DM) is reported to increase the risk for dementia, including AD, but the underlying mechanism is not understood. Here, we investigated the brain insulin-PI3K-AKT signalling pathway in the autopsied frontal cortices from nine AD, 10 T2DM, eight T2DM-AD and seven control cases. We found decreases in the levels and activities of several components of the insulin-PI3K-AKT signalling pathway in AD and T2DM cases. The deficiency of insulin-PI3K-AKT signalling was more severe in individuals with both T2DM and AD (T2DM-AD). This decrease in insulin-PI3K-AKT signalling could lead to activation of glycogen synthase kinase-3β, the major tau kinase. The levels and the activation of the insulin-PI3K-AKT signalling components correlated negatively with the level of tau phosphorylation and positively with protein O-GlcNAcylation, suggesting that impaired insulin-PI3K-AKT signalling might contribute to neurodegeneration in AD through down-regulation of O-GlcNAcylation and the consequent promotion of abnormal tau hyperphosphorylation and neurodegeneration. The decrease in brain insulin-PI3K-AKT signalling also correlated with the activation of calpain I in the brain, suggesting that the decrease might be caused by calpain over-activation. Our findings provide novel insight into the molecular mechanism by which type 2 diabetes mellitus increases the risk for developing cognitive impairment and dementia in Alzheimer's disease.
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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.