ArticleJournal of Alzheimer's disease : JAD2012
Long-term pioglitazone treatment improves learning and attenuates pathological markers in a mouse model of Alzheimer's disease.
Article in Journal of Alzheimer's disease : JAD, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 2 of them syntheses that pooled it.
What it found
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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
84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 152 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 diabetes medications on the risk of developing dementia, mild cognitive impairment, or cognitive decline: A systematic review and meta-analysis.Journal of Alzheimer's disease : JAD · 2025Pooled it
- Pioglitazone protects against trimethyltin hippocampal injury by reducing pyroptosis, mitochondrial dysregulation and ER stress.Scientific reports · 2026Article
- The metabolic roots of memory loss: interlinking the Diabetes-Alzheimer's hypothesis.Metabolic brain disease · 2026Review
- Restoration neurite growth by removing the blockage of endosome trafficking in Alzheimer-like mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Insights into therapeutic approaches for the treatment of neurodegenerative diseases targeting metabolic syndrome.Molecular biology reports · 2025Review
- Histone Methylation, Energy Metabolism, and Alzheimer's Disease.Aging and disease · 2024Review
- Single-nucleus RNA sequencing-based construction of a hippocampal neuron atlas in mice with epileptic cognitive impairment.iScience · 2024Article
- PPARγ activation ameliorates cognitive impairment and chronic microglial activation in the aftermath of r-mTBI.Journal of neuroinflammation · 2024Article
- PPARs (Peroxisome Proliferator-activated Receptors) and Their Agonists in Alzheimer's Disease.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2024Review
- Long-Term Pioglitazone Treatment Has No Significant Impact on Microglial Activation and Tau Pathology in P301S Mice.International journal of molecular sciences · 2023Article
- Review
- Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke.Neurology · 2023Article
- Selective PPAR-Delta/PPAR-Gamma Activation Improves Cognition in a Model of Alzheimer's Disease.Cells · 2023Article
- Revealing genetic links of Type 2 diabetes that lead to the development of Alzheimer's disease.Heliyon · 2023Article
- The Therapeutic Potential of Mitochondria Transplantation Therapy in Neurodegenerative and Neurovascular Disorders.Current neuropharmacology · 2023Review
- Review
- A Pathophysiological Intersection of Diabetes and Alzheimer's Disease.International journal of molecular sciences · 2022Review
- Therapeutic strategies for tauopathies and drug repurposing as a potential approach.Biochemical pharmacology · 2022Review
- Dysmetabolism and Neurodegeneration: Trick or Treat?Nutrients · 2022Review
24 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
13 authors at 2 institutions in 1 country.
Funding
Abstract
Thiazolidinediones (TZDs) are agonists at peroxisome proliferator-activated gamma-type (PPAR-γ) receptors and are used clinically for the treatment of type 2 diabetes where they have been shown to reestablish insulin sensitivity, improve lipid profiles, and reduce inflammation. Recent work also suggests that TZDs may be beneficial in Alzheimer's disease (AD), ameliorating cognitive decline early in the disease process. However, there have been only a few studies identifying mechanisms through which cognitive benefits may be exerted. Starting at 10 months of age, the triple transgenic mouse model of AD (3xTg-AD) with accelerated amyloid-β (Aβ) deposition and tau pathology was treated with the TZD pioglitazone (PIO-Actos) at 18 mg/Kg body weight/day. After four months, PIO-treated animals showed multiple beneficial effects, including improved learning on the active avoidance task, reduced serum cholesterol, decreased hippocampal amyloid-β and tau deposits, and enhanced short- and long-term plasticity. Electrophysiological membrane properties and post-treatment blood glucose levels were unchanged by PIO. Gene microarray analyses of hippocampal tissue identified predicted transcriptional responses following TZD treatment as well as potentially novel targets of TZDs, including facilitation of estrogenic processes and decreases in glutamatergic and lipid metabolic/cholesterol dependent processes. Taken together, these results confirm prior animal studies showing that TZDs can ameliorate cognitive deficits associated with AD-related pathology, but also extend these findings by pointing to novel molecular targets in the brain.
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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.