Chronic melatonin therapy fails to alter amyloid burden or oxidative damage in old Tg2576 mice:: Implications for clinical trials

Melatonin has been proposed as a treatment for Alzheimer's disease based on the demonstration of antioxidant and "anti-amyloid' effects in vitro and in vivo. Chronic melatonin therapy in old, amyloid plaque-bearing transgenic mice was studied. Tg2576 mice started melatonin treatment at 14 months of age. After 4 months of treatment, there were no differences between untreated and melatonin-treated mice in cortical levels of soluble, formic acid extracted, or histologically detectable beta amyloid (A), nor in brain levels of lipid peroxidation product (total 8,12-isoprostane F-2 alpha-VI), despite marked elevations in plasma melatonin. We conclude that melatonin fails to produce antiamyloid or antioxidant effects when initiated after the age of amyloid plaque deposition. These findings diminish the possibility that melatonin will be useful for the treatment of established Alzheimer's disease. (c) 2005 Elsevier B.V. All rights reserved.