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 (Aβ), nor in brain levels of lipid peroxidation product (total 8,12-isoprostane F_2α-VI), despite marked elevations in plasma melatonin. We conclude that melatonin fails to produce anti-amyloid 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.