ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2023
Metformin Attenuates Tau Pathology in Tau-Seeded PS19 Mice.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies.Molecular neurodegeneration · 2025Pooled it
- Early cerebral hypoperfusion promotes spatially biased tau pathology in tau-seeded PS19 mice.GeroScience · 2026Article
- Cofilin-1 Exacerbates Tau-Induced Mitochondrial Damage, Oxidative Stress, and Apoptosis in Alzheimer's Disease.Neurochemical research · 2026Article
- Metformin for Longevity and Sarcopenia: A Therapeutic Paradox in Aging.Biomedicines · 2026Article
- Emerging roles for innate and adaptive immunity in tauopathies.Cell reports · 2025Review
- 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
- Hampered AMPK-ULK1 cascade in Alzheimer's disease (AD) instigates mitochondria dysfunctions and AD-related alterations which are alleviated by metformin.Alzheimer's research & therapy · 2025Article
- Noninvasive Detection of Oxidative Stress in a Mouse Model of 4R Tauopathy via Positron Emission Tomography with [International journal of molecular sciences · 2025Article
- Mechanism and Clinical Application Prospects of Mitochondrial DNA Single Nucleotide Polymorphism in Neurodegenerative Diseases.Neurochemical research · 2024Review
- Should We Consider Neurodegeneration by Itself or in a Triangulation with Neuroinflammation and Demyelination? The Example of Multiple Sclerosis and Beyond.International journal of molecular sciences · 2024Review
- Therapeutic Effects of Metformin on Central Nervous System Diseases: A Focus on Protection of Neurovascular Unit.Pharmaceutical research · 2024Review
- Postencephalitic Parkinsonism: Unique Pathological and Clinical Features-Preliminary Data.Cells · 2024Article
- Article
- How close is autophagy-targeting therapy for Alzheimer's disease to clinical use? A summary of autophagy modulators in clinical studies.Frontiers in cell and developmental biology · 2024Review
- Critical thinking of Alzheimer's transgenic mouse model: current research and future perspective.Science China. Life sciences · 2023Review
- Does modulation of tau hyperphosphorylation represent a reasonable therapeutic strategy for Alzheimer's disease? From preclinical studies to the clinical trials.Molecular psychiatry · 2023Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau is a histopathological hallmark of Alzheimer's disease (AD) and related tauopathies. Growing evidence demonstrated that tau pathology in AD spreads in a prion-like manner. Previous studies showed that metformin might have a positive effect on cognition. However, the underlying mechanisms are still unknown. Therefore, the present study aimed to investigate the effects of metformin on tau propagation. Brain extracts containing tau aggregates were unilaterally injected into the hippocampus and the overlying cerebral cortex of PS19 mice. Metformin was administrated through drinking water for four months, and we observed tau spreading in the brain of tau-seeded PS19 mice. Metformin inhibited the spreading of tau pathology in the ipsilateral hemisphere, attenuated tau pathology in the contralateral hemisphere, and reduced the hyperphosphorylation of tau at Ser202/Thr205, Thr231, and Ser422 sites in the soluble fraction and Ser202/Thr205, Ser262, Thr396, Thr231, and Ser422 sites in the insoluble fraction of tau-seeded PS19 mice brains. Metformin did not affect tau kinases or phosphatase 2A protein levels but reduced mTORC1 protein levels. Additionally, metformin reduced learning and memory deficits of the tau-seeded PS19 mice. These findings indicate that metformin reduced tau hyperphosphorylation, attenuated tau pathology in tau-seeded PS19 mice, and improved learning and memory deficits. These findings highlight the potential mechanisms underlying the beneficial effects of metformin on cognition, implying that metformin could be a promising drug for the prevention and early treatment of AD.
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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.