Evidence of oxidative stress in Alzheimer's disease brain and antioxidant therapy: lights and shadows.
Alzheimer's disease (AD) is the most common form of neurodegenerative disease associated with dementia in the elderly. Although the initiating events are still unknown, it is clear that AD, at least in its sporadic form, results from the combination of genetic risk factors with different epigenetic events. Among them, a growing body of evidence suggests that an imbalance between free radical formation and destruction is involved in AD pathogenesis. This concept originally derived from the free radical hypothesis of aging, which states that the age-related accumulation of free radicals results in damaged cell components. The fact that age is a key risk factor in AD provides support for this hypothesis. There is a long list of surrogate markers, which includes lipid, DNA, and protein oxidation, of oxidant stress-mediated injury that have been reported as elevated in the AD brain. Moreover, epidemiologic studies show that dietary intake of natural or synthetic products with a putative antioxidant effect, such as (but not only) vitamin E, reduces the risk of AD. On the other hand, antioxidative intervention studies in animal models of AD-like amyloidosis show a significant reduction in amyloid beta deposition and behavioral improvements. However, a randomized clinical trial of vitamin E supplementation in AD patients shows only a marginal positive effect. Another study reports no effect of vitamin E on the rate of progression of AD in subjects with mild cognitive impairment. This article will review both promises and caveats of the available data and propose future directions to be taken for addressing them.
Praticò
Domenico
D
Department of Pharmacology, Temple University, School of Medicine, Philadelphia, PA 19140, USA. praticod@temple.edu
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D018849:Controlled Clinical Trials as Topic; D006801:Humans; D018384:Oxidative Stress; D011446:Prospective Studies
D000975:Antioxidants