ArticleExperimental brain research2021
Metformin prevents p-tau and amyloid plaque deposition and memory impairment in diabetic mice.
Article in Experimental brain research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies.Molecular neurodegeneration · 2025Pooled it
- Effect of Metformin on Plasma and Cerebrospinal Fluid Biomarkers in Non-Diabetic Older Adults with Mild Cognitive Impairment Related to Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Trial
- Unlocking the aging brain: mTORC1 as a convergent integrator for neurodegeneration and therapeutic intervention.Biogerontology · 2026Review
- Metformin Ameliorates Cognitive Deficits and Neuroinflammation in a Mouse Model of Familial Hypercholesterolemia.Neurochemical research · 2026Article
- Pharmacological modulation of the PI3K/AKT/GSK3β axis: a new frontier in Alzheimer's disease treatment.Inflammopharmacology · 2026Review
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- Neuroprotective Roles of Metformin in a Streptozotocin-Induced Dementia Model in Rats.Neurotoxicity research · 2025Article
- Targeting of the PI3 K/AKT/GSK3β Pathway in Parkinson's Disease: A Therapeutic Blueprint.Molecular neurobiology · 2025Review
- From Diabetes to Degenerative Diseases: The Multifaceted Action of Metformin.International journal of molecular sciences · 2025Review
- Low-Dose Intranasal Metformin Exerts Neuroprotective Effects in a Rat Model of Sporadic Alzheimer's Disease.Molecular neurobiology · 2025Article
- Metformin Improves Spatial Memory and Reduces Seizure Severity in a Rat Model of Epilepsy and Alzheimer's Disease comorbidity via PI3K/Akt Signaling Pathway.Molecular neurobiology · 2025Article
- The metformin administration on pancreatic tissue damage in metastatic rat prostate cancer and STZ induced diabetes model.Journal of molecular histology · 2025Article
- Combined Administration of Metformin and Propionate Reduces the Degree of Oxidative/Nitrosative Damage of Hypothalamic Neurons in Rat Model of Type 2 Diabetes Mellitus.Molecular neurobiology · 2025Article
- The mechanism underlying streptozotocin injection for the development of a nontransgenic Alzheimer's disease animal model.Open veterinary journal · 2025Review
- Metformin and the PI3K/AKT signaling pathway: implications for cancer, cardiovascular, and central nervous system diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Metformin improves age-related visual cortex dysfunction in mice by reducing noise correlation in the primary visual cortex.Frontiers in aging neuroscience · 2025Article
- The Diabetic Cognitive Impairment Score for Early Screening of Cognitive Impairment in Type 2 Diabetes Patients.Journal of diabetes research · 2025Article
- Curcumin and Metformin Infinite Coordination Polymer Nanoparticles for Combined Therapy of Diabetic Mice via Intraperitoneal Injections.Journal of functional biomaterials · 2024Article
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Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Insulin deficiency or resistance can promote dementia and hallmarks of Alzheimer's disease (AD). The formation of neurofibrillary tangles of p-TAU protein, extracellular Aβ plaques, and neuronal loss is related to the switching off insulin signaling in cognition brain areas. Metformin is a biguanide antihyperglycemic drug used worldwide for the treatment of type 2 diabetes. Some studies have demonstrated that metformin exerts neuroprotective, anti-inflammatory, anti-oxidant, and nootropic effects. This study aimed to evaluate metformin's effects on long-term memory and p-Tau and amyloid β modulation, which are hallmarks of AD in diabetic mice. Swiss Webster mice were distributed in the following experimental groups: control; treated with streptozotocin (STZ) that is an agent toxic to the insulin-producing beta cells; STZ + metformin 200 mg/kg (M200). STZ mice showed significant augmentation of time spent to reach the target box in the Barnes maze, while M200 mice showed a significant time reduction. Moreover, the M200 group showed reduced GFAP immunoreactivity in hippocampal dentate gyrus and CA1 compared with the STZ group. STZ mice showed high p-Tau levels, reduced p-CREB, and accumulation of β-amyloid (Aβ) plaque in hippocampal areas and corpus callosum. In contrast, all these changes were reversed in the M200 group. Protein expressions of p-Tau, p-ERK, pGSK3, iNOS, nNOS, PARP, Cytochrome c, caspase 3, and GluN2A were increased in the parietal cortex of STZ mice and significantly counteracted in M200 mice. Moreover, M200 mice also showed significantly high levels of eNOS, AMPK, and p-AKT expression. In conclusion, metformin improved spatial memory in diabetic mice, which can be associated with reducing p-Tau and β-amyloid (Aβ) plaque load and inhibition of neuronal death.
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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.