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 (Abeta), nor in brain levels of lipid peroxidation product (total 8,12-isoprostane F(2alpha)-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.
Quinn
Joseph
J
Portland Veteran's Affairs Medical Center, Department of Neurology, Portland, OR 97239, USA. quinnj@ohsu.edu
Kulhanek
Doris
D
Nowlin
Jessica
J
Jones
Richard
R
Praticò
Domenico
D
Rokach
Joshua
J
Stackman
Robert
R
D000375:Aging / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001253:Astrocytes / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008550:Melatonin / Q000097:blood / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D058225:Plaque, Amyloid / Q000473:pathology*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D008550:Melatonin