Sung Syuan, Yao Yuemang, Uryu Kunihiro, Yang Hengxuan, Lee Virginia M-Y, Trojanowski John Q, Praticò Domenico
Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
FASEB J. 2004 Feb;18(2):323-5. doi: 10.1096/fj.03-0961fje. Epub 2003 Dec 4.
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.
脑氧化应激增加是阿尔茨海默病（AD）的一个关键特征，主要表现为脂质过氧化。然而，抗氧化剂能够影响该疾病临床进程的临床证据有限。在本研究中，我们研究了抗氧化剂维生素E在淀粉样斑块沉积之前或之后给予AD转基因小鼠模型（Tg2576）时，对AD样表型的影响。一组Tg2576小鼠从5月龄开始接受维生素E直至13月龄，第二组从14月龄开始接受维生素E直至20月龄。与给予安慰剂的小鼠相比，接受维生素E的两组小鼠脑中脂质过氧化的特异性标志物8,12-异前列腺素F2α-VI的水平均显著降低。在较年轻时给予维生素E的Tg2576小鼠，其β淀粉样蛋白（Aβ）水平和淀粉样沉积显著减少。相比之下，在较晚年龄接受补充维生素E饮食的小鼠与给予安慰剂的小鼠相比，在任何一个标志物上均未显示出显著差异。这些结果支持了以下假说：氧化应激是AD发病机制中的一个重要早期事件，并且抗氧化治疗可能仅在疾病进程的这一阶段给予才有益。
