Early vitamin E supplementation in young but not aged mice reduces Abeta levels and amyloid deposition in a transgenic model of Alzheimer's disease.
Increased brain oxidative stress is a key feature of Alzheimer's disease (AD) and manifests predominantly as lipid peroxidation. However, clinical evidence that antioxidants can affect the clinical course of the disease is limited. In the present study, we investigated the effect of the antioxidant Vitamin E on the AD-like phenotype when given to a transgenic mouse model (Tg2576) of the disease before or after the amyloid plaques are deposited. One group of Tg2576 received Vitamin E starting at 5 months of age until they were 13 months old, the second group started at 14 months of age until they were 20 months old. Brain levels of 8,12-iso-iPF2alpha-VI, a specific marker of lipid peroxidation, were significantly reduced in both groups of mice receiving Vitamin E compared with placebo. Tg2576 administered with Vitamin E at a younger age showed a significant reduction in Abeta levels and amyloid deposition. By contrast, mice receiving the diet supplemented with Vitamin E at a later age did not show any significant difference in either marker when compared with placebo. These results support the hypothesis that oxidative stress is an important early event in AD pathogenesis, and antioxidant therapy may be beneficial only if given at this stage of the disease process.
Sung
Syuan
S
Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Yao
Yuemang
Y
Uryu
Kunihiro
K
Yang
Hengxuan
H
Lee
Virginia M-Y
VM
Trojanowski
John Q
JQ
Praticò
Domenico
D
D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000178:diet therapy* / Q000378:metabolism / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000686:Amyloidosis / Q000178:diet therapy / Q000517:prevention & control; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D018450:Disease Progression; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D014810:Vitamin E