Triterpenoid CDDO-methylamide improves memory and decreases amyloid plaques in a transgenic mouse model of Alzheimer's disease |
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| Authors: | Magali Dumont Elizabeth Wille Noel Y Calingasan Davide Tampellini Charlotte Williams† Gunnar K Gouras Karen Liby† Michael Sporn† M Flint Beal Michael T Lin |
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| Institution: | Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, New York, USA;
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, USA |
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| Abstract: | Oxidative stress is one of the earliest events in the pathogenesis of Alzheimer's disease (AD) and can markedly exacerbate amyloid pathology. Modulation of antioxidant and anti-inflammatory pathways represents an important approach for AD therapy. Synthetic triterpenoids have been found to facilitate antioxidant response and reduce inflammation in several models. We investigated the effect of the triterpenoid, 2-Cyano-3,12-Dioxooleana-1,9-Dien-28-Oic acid-MethylAmide (CDDO-MA) in Tg19959 mice, which carry the human amyloid precursor protein with two mutations. These mice develop memory impairments and amyloid plaques as early as 2–3 months of age. CDDO-MA was provided with chow (800 mg/kg) from 1 to 4 months of age. CDDO-MA significantly improved spatial memory retention and reduced plaque burden, Aβ42 levels, microgliosis, and oxidative stress in Tg19959 mice. |
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| Keywords: | Alzheimer's disease amyloid antioxidant memory oxidative stress triterpenoid |
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