ArticleThe Journal of biological chemistry2015
Combined Liver X Receptor/Peroxisome Proliferator-activated Receptor γ Agonist Treatment Reduces Amyloid β Levels and Improves Behavior in Amyloid Precursor Protein/Presenilin 1 Mice.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis 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.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Effect of antidiabetic drugs in Alzheimer´s disease: a systematic review of preclinical and clinical studies.Molecular neurodegeneration · 2025Pooled it
- Brain Single-Cell Transcriptional Responses to Bexarotene-Activated RXR in an Alzheimer's Disease Model.International journal of molecular sciences · 2026Article
- Unraveling changes in mitochondrial processes influenced by ancestry inFrontiers in aging neuroscience · 2026Article
- LC-MS/MS-Profiling of Human Serum Unveils Significant Increase in Neuroinflammation and Carcinogenesis Following Chronic Organophosphate Exposure.Journal of proteome research · 2025Article
- Enhancing of cerebral Abeta clearance by modulation of ABC transporter expression: a review of experimental approaches.Frontiers in aging neuroscience · 2024Review
- High glucose inhibits neural differentiation by excessive autophagy <em>via</em> peroxisome proliferator-activated receptor gamma.European journal of histochemistry : EJH · 2023Article
- The small HDL particle hypothesis of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Role of Oxysterols in the Activation of the NLRP3 Inflammasome as a Potential Pharmacological Approach in Alzheimer's Disease.Current neuropharmacology · 2023Review
- Astrocytes as a Therapeutic Target in Alzheimer's Disease-Comprehensive Review and Recent Developments.International journal of molecular sciences · 2022Review
- Diabetes: Risk factor and translational therapeutic implications for Alzheimer's disease.The European journal of neuroscience · 2022Article
- HDL-like-Mediated Cell Cholesterol Trafficking in the Central Nervous System and Alzheimer's Disease Pathogenesis.International journal of molecular sciences · 2022Review
- Remembering your A, B, C's: Alzheimer's disease and ABCA1.Acta pharmaceutica Sinica. B · 2022Review
- Network Pharmacology and Molecular Docking-Based Strategy to Investigate the Multitarget Mechanisms of Shenqi Yizhi Granule on Alzheimer's Disease.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Microglial Function and Regulation during Development, Homeostasis and Alzheimer's Disease.Cells · 2021Review
- Reassessment of Pioglitazone for Alzheimer's Disease.Frontiers in neuroscience · 2021Review
- The Janus-like Association between Proton Pump Inhibitors and Dementia.Current Alzheimer research · 2021Article
- Clinical Evidence of Antidepressant Effects of Insulin and Anti-Hyperglycemic Agents and Implications for the Pathophysiology of Depression-A Literature Review.International journal of molecular sciences · 2020Review
- Alzheimer's Disease, a Lipid Story: Involvement of Peroxisome Proliferator-Activated Receptor α.Cells · 2020Review
- Molecular Insight into the Therapeutic Promise of TargetingOxidative medicine and cellular longevity · 2020Review
- Is Alzheimer's Disease a Liver Disease of the Brain?Journal of Alzheimer's disease : JAD · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Alzheimer disease (AD) is characterized by the extracellular accumulation of amyloid β (Aβ), which is accompanied by a robust inflammatory response in the brain. Both of these pathogenic processes are regulated by nuclear receptors, including the liver X receptors (LXRs) and peroxisome-proliferator receptor γ (PPARγ). Agonists of LXRs have been demonstrated previously to reduce Aβ levels and improve cognitive deficits in AD mouse models by inducing the transcription and lipidation of apolipoprotein E (apoE). Agonists targeting PPARγ reduce the microglial expression of proinflammatory genes and have also been shown to modulate apoE expression. Here we investigate whether a combination therapy with both LXR and PPARγ agonists results in increased benefits in an AD mouse model. We found that the LXR agonist GW3965 and the PPARγ agonist pioglitazone were individually able to increase the levels of apoE and related genes, decrease the expression of proinflammatory genes, and facilitate Aβ decreases in the hippocampus. Combined treatment with both agonists provoked a further increase in the expression of apoE and a decrease in the soluble and deposited forms of Aβ. The decrease in plaques was associated with increased colocalization between microglia and plaques. In addition, the PPARγ agonist in the combined treatment paradigm was able to counteract the elevation in plasma triglycerides that is a side effect of LXR agonist treatment. These results suggest that combined LXR/PPARγ agonist treatment merits further investigation for the 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.