Rosiglitazone rescues memory impairment in Alzheimer’s transgenic mice: Mechanisms involving a reduced amyloid and tau pathology
Open accessAbstract
Clinical studies suggest that agonists at peroxisome proliferator-activated receptor gamma (PPARgamma) may exert beneficial effects in patients with mild-to-moderate Alzheimer's disease (AD), but the mechanism for the potential therapeutic interest of this class of drugs has not yet been elucidated. Here, in mice overexpressing mutant human amyloid precursor protein, we found that chronic treatment with rosiglitazone, a high-affinity agonist at PPARgamma, facilitated beta-amyloid peptide (Abeta) clearance. Rosiglitazone not only reduced Abeta burden in the brain but, importantly, almost completely removed the abundant amyloid plaques observed in the hippocampus and entorhinal cortex of 13-month-old transgenic mice. In the hippocampus, neuropil threads containing phosphorylated tau, probably corresponding to dystrophic neurites, were also decreased by the drug. Rosiglitazone switched on the activated microglial phenotype, promoting its phagocytic ability, reducing the expression of proinflammatory markers and inducing factors for alternative differentiation. The decreased amyloid pathology may account for the reduction of p-tau-containing neuropil threads and for the rescue of impaired recognition and spatial memory in the transgenic mice. This study provides further insights into the mechanisms for the beneficial effect of rosiglitazone in AD patients.
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Stimulation of insulin signaling protects against accumulation of hyperphosphorylated tau, a pathological hallmark of Alzheimer's disease that is induced by Aβ oligomers.
“stimulation of insulin signaling also protects against accumulation of hyperphosphorylated tau (Escribano et al., 2010), a pathological hallmark of AD that is induced by Aβ oligomers (De Felice et al., 2008).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Escribano et al., 2010
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References 56 · Cited by 235
- Authors
- Escribano, L., Simón, A.-M., Gimeno, E., Cuadrado-Tejedor, M., López de Maturana, R., García-Osta, A., Ricobaraza, A., Pérez-Mediavilla, A., Del Río, J., & Frechilla, D.
- Affiliations
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Corresponding author
- Frechilla, Diana
- ORCID
- Ricobaraza, Ana
- Venue
- Neuropsychopharmacology
- Published
- 2010-03-24
- Volume
- 35
- Issue
- 7
- Pages
- 1593-1604
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3055461
- OpenAlex
- W2083579642
- Cited by
- 235
- References
- 56
- Citations by year
- 2026: 3 · 2025: 18 · 2024: 19 · 2023: 12 · 2022: 12 · 2021: 16 · 2020: 27 · 2019: 19 · 2018: 17 · 2017: 9 · 2016: 16 · 2015: 9 · 2014: 21 · 2013: 12 · 2012: 14
- FWCI
- 8.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion, other-oa)
- Funders
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- rosiglitazone, Alzheimer's disease, PPARγ agonists, amyloid-beta clearance, amyloid plaques, tau phosphorylation, neuropil threads, microglial activation, pro-inflammatory markers, memory impairment, amyloid precursor protein transgenic mice, hippocampus, entorhinal cortex
- MeSH terms
- Rosiglitazone, Alzheimer Disease, Analysis of Variance, Animals, Gene Expression Regulation, Humans, Hypoglycemic Agents, Memory Disorders, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Neuropsychological Tests, Peptide Fragments, Cytokines, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, tau Proteins, Maze Learning, CD36 Antigens, Recognition, Psychology, CD11b Antigen, Thiazolidinediones, Mice, Cyclooxygenase 2
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