Two potential therapies using antioxidant compounds – one found in red grapes and another found in leafy green vegetables – are among Alzheimer's disease studies being supported this year by Oregon's tax check-off funds.
The Oregon Alzheimer's Disease Research Small Grants Program, funded by Oregon residents who donate portions of their state tax refunds toward Alzheimer's disease research, provides grants up to $25,000 for projects by Oregon investigators. The grant period is from Aug. 1, 2007, to July 31, 2008. All of this year's grants are worth $25,000.
One of this year's studies is by investigators Wei Wang, Ph.D., nutritionist and research assistant professor of medicine (endocrinology, diabetes and clinical nutrition), and Joseph Quinn, M.D., associate professor neurology, Oregon Health & Science University School of Medicine. They will examine whether supplementation of lutein, a main carotenoid found in leafy green vegetables, can effectively reduce oxidative damage in Alzheimer's disease patients. Lutein has been strongly associated with the reduction of the risk of age-related macular degeneration, a common eye disease leading to blindness in elderly population.
"From previous research on lutein and age-related macular degeneration, I have realized that lutein, a fat-soluble antioxidant belonging to carotenoid family, has special physical and chemical properties that could potentially be very important for brain function," Wang said.
Oxidative damage is thought to be a major factor in cognitive decline during the aging process and Alzheimer's disease. Carotenoids are known to reduce oxidative damage, but "so far have not been studied as an antioxidant therapy in reducing oxidative damage in Alzheimer patients," Wang said.
Quinn said lutein's antioxidant action is believed to prevent the "biological rust" associated with Alzheimer's. "It is attractive for AD because it specifically protects fats from oxidation, and the brain is mostly fat," he said. "There are many physiological similarities between retina and brain, including the presence of a 'blood-brain barrier' and a 'blood-retina barrier,' which exclude many potential treatments from the intended site of action."
Previous studies have shown that moderately severe Alzheimer's patients had significantly lower blood levels of some major carotenoids, including lutein, compared with healthy elderly persons. "Lutein supplementation has been shown to reduce damage from free radicals in healthy elderly who have low blood carotenoid levels. We expect to see similar positive effects of lutein supplementation on reduction of oxidative damage in Alzheimer patients," Wang said.
Another study co-investigated by Quinn and Teri Wadsworth, Ph.D., OHSU research assistant professor of neurology, is looking at antioxidant effects that different concentrations of resveratrol, a natural compound of red grapes, have on beta amyloid, the protein that clumps to form plaques that kill brain cells, leading to Alzheimer's. In addition to possessing antioxidant properties, Resveratrol is thought to activate an enzyme called SIRT1 that protects brain cells from amyloid-induced death.
"Resveratrol is distinct from most other current AD prevention strategies because it has shown 'anti-aging' effects in a number of model systems," Quinn said. "Although age is the strongest risk factor for the development of AD, most current treatment strategies are focused on other mechanisms, like the amyloid in plaques."
Wadsworth and Quinn want to develop techniques for monitoring SIRT1 activation in human white blood cells so it can be used in future clinical trials as a biomarker for resveratrol's effects. By differentiating the mechanisms by which resveratrol exerts anti-amyloid effects, they also hope to develop molecular targets for preventing and treating Alzheimer's.
Oregon Alzheimer's Disease Research Small Grants recipients are determined by the Oregon Partnership for Alzheimer's Research, an alliance of scientists and administrators from OHSU, Providence Health System in Oregon, Kaiser Permanente, Salem Alzheimer's Network, Portland State University, University of Oregon, and Oregon State University. The Layton Aging & Alzheimer's Disease Center serves as steward for the program's funds.
Linda Boise, Ph.D., M.P.H., associate professor of neurology, OHSU School of Medicine, and the Layton Center's director of education and information, said this year's projects speak to the value of Oregon's support for Alzheimer's research. "We didn't get as large a number of applicants as in previous years, but the ones we got were very high quality," she said.
Grants are awarded to clinical investigators and basic scientists for clinical, biological, behavioral or health system research that will advance understanding, treatment and prevention of Alzheimer's disease. Appropriate fields include the neurosciences, nursing, social work, epidemiology, sociology, psychology, psychiatry, economics, counseling, delivery of health care services and others relevant to Alzheimer's research or practice. Applicants are evaluated on scientific merit, but priority is given to investigators just entering the field of dementia research and to new or innovative projects.
Other recipients of Alzheimer's disease research small grants include:
• "Apolipoprotein conformational changes in Alzheimer's disease," Randall L. Woltjer, M.D., Ph.D., assistant professor of pathology, OHSU School of Medicine.
• "Keys to optimal cognitive aging: Comparisons of social engagement and network, and nutrition between elderly Oregonians and Okinawans," Hiroko Dodge, Ph.D., assistant professor of public health, Oregon State University.
• "Seeking common ground: Family caregiver appraisal of communication problems in persons with AD," Jeon Small, research associate and graduate student, OHSU Child Development & Rehabilitation Center, and Melanie Fried-Oken, Ph.D., associate professor of neurology, OHSU School of Medicine.
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