Antioxidant strategies for Alzheimer's disease.
Oxidative damage is present within the brains of patients with Alzheimer's disease (AD), and is observed within every class of biomolecule, including nucleic acids, proteins, lipids and carbohydrates. Oxidative injury may develop secondary to excessive oxidative stress resulting from beta-amyloid-induced free radicals, mitochondrial abnormalities, inadequate energy supply, inflammation or altered antioxidant defences. Treatment with antioxidants is a promising approach for slowing disease progression to the extent that oxidative damage may be responsible for the cognitive and functional decline observed in AD. Although not a uniformly consistent observation, a number of epidemiological studies have found a link between antioxidant intake and a reduced incidence of dementia, AD and cognitive decline in elderly populations. In AD clinical trials molecules with antioxidant properties such as vitamin E and Ginkgo biloba extract have shown modest benefit. A clinical trial with vitamin E is currently ongoing to determine if it can delay progression to AD in individuals with mild cognitive impairment. Combinations of antioxidants might be of even greater potential benefit for AD, especially if the agents worked in different cellular compartments or had complementary activity (e.g. vitamins E, C and ubiquinone). Naturally-occurring compounds with antioxidant capacity are available and widely marketed (e.g. vitamin C, ubiquinone, lipoic acid, beta-carotene, creatine, melatonin, curcumin) and synthetic compounds are under development by industry. Nevertheless, the clinical value of these agents for AD prevention and treatment is ambiguous, and will remain so until properly designed human trials have been performed.
Grundman
Michael
M
Alzheimer's Disease Cooperative Study, University of California, San Diego, 8950 Villa La Jolla Drive, Suite 2200, La Jolla, California 92037, USA. mgrundman@ucsd.edu
Grundman
Michael
M
Delaney
Patrick
P
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000517:prevention & control; D000975:Antioxidants / Q000627:therapeutic use*; D019587:Dietary Supplements; D018450:Disease Progression; D004359:Drug Therapy, Combination; D020441:Ginkgo biloba; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D014810:Vitamin E / Q000627:therapeutic use
D000975:Antioxidants; D014810:Vitamin E