Sanders-Brown Receives NIH Funding
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LEXINGTON, Ky. (May 5, 2008) − The University of Kentucky Sanders-Brown Center on Aging,
under the leadership of Dr. William R. Markesbery, director of the center and its
Alzheimer’s Disease Center, Commonwealth Chair in Aging, and professor of pathology and
neurology in the UK College of Medicine, has received two major grants from the National
Institutes of Health's (NIH) National Institute on Aging (NIA).
"It is a difficult funding period at the National Institutes of Health and we are fortunate to receive these grants," said Markesbery. "I credit the team effort and hard work of the Sanders-Brown Center investigators who made the awarding of these grants possible.”
The first study is the NIH/NIA program project grant, “Beta Amyloid and Oxidative Stress in Alzheimer’s Disease,” which was funded in the amount of $1.8 million annually for 5 years. This program project grant has been funded for 20 years and this latest award is for years 20 through 25. The study is composed of three cores and four projects.
According to Markesbery, the principal investigator for the study, the major hypothesis of the research is that beta-amyloid peptide (Aβ), present in the form of senile plaques in the brain in Alzheimer’s disease (AD), is thought to be a critical alteration involved in oxidative damage to neurons. The project will use autopsied brain specimens from subjects with preclinical AD, patients with mild cognitive impairment and late stage AD, normal control subjects, a transgenic animal model of amyloidosis (APP/PS1 knock-in mice), and cultured neurons and glia to study Aβ-mediated RNA oxidation as an early event in AD that interferes with protein synthesis and neuron degeneration.. It will also investigate whether Aβ-mediated oxidation of specific proteins cause some of the pathological features of AD; elevated advanced glycation end products-ligand interaction with Aβ is an important process in the progression of AD; and Aβ activation of NADPH oxidase triggers a cascade linking increased free radicals to altered redox-based signaling and neurotoxic oxidative damage. The goal of the studies is to gain a better basic understanding of AD and identify novel therapeutic strategies which could lead to treatment of AD.
Other Sanders-Brown researchers for the study include: Mark Lovell, associate professor of chemistry, UK College of Arts and Sciences and Paul Murphy, assistant professor, and Harry LeVine, associate professor, Department of Molecular and Cellular Biochemistry, UK College of Medicine. Additional UK faculty include Daret St. Clair, professor, UK Graduate Center for Toxicology and Alan Butterfield, professor of chemistry, UK College of Arts and Sciences. Two researchers from the Pennington Biomedical Research Center at Louisiana State University also are participating. They are Anna Bruce-Keller, associate professor, and Jeff Keller, associate executive director for basic research.
The second study, previously funded for years 1-6 and now renewed for years 7-12, is “The Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADVISE).” It is funded for $1.3 million annually and is the largest AD prevention trial in the country.
The PREADVISE study is an important addition to the National Cancer Institute’s Selenium and Vitamin E Cancer Prevention Trial (SELECT). The purpose of PREADVISE is to determine if taking selenium and/or vitamin E supplements can prevent AD and other less common forms of dementia. Markesbery is the principal investigator and Dr. Frederick Schmitt, professor of neurology, UK College of Medicine, and Richard Kryscio, professor of statistics, UK College of Public Health, are the co-principal investigators. Currently more than 6,500 men have elected to take part in PREADVISE.
"The point in this study is to prevent Alzheimer's disease," said Markesbery. "We are studying men age 60 to 65 and older who are in good health at entry into the study."
In the PREADVISE study, some participants will receive vitamin E; some receive selenium; some receive a mix of both vitamin E and selenium; and others receive a placebo.
"It is a difficult funding period at the National Institutes of Health and we are fortunate to receive these grants," said Markesbery. "I credit the team effort and hard work of the Sanders-Brown Center investigators who made the awarding of these grants possible.”
The first study is the NIH/NIA program project grant, “Beta Amyloid and Oxidative Stress in Alzheimer’s Disease,” which was funded in the amount of $1.8 million annually for 5 years. This program project grant has been funded for 20 years and this latest award is for years 20 through 25. The study is composed of three cores and four projects.
According to Markesbery, the principal investigator for the study, the major hypothesis of the research is that beta-amyloid peptide (Aβ), present in the form of senile plaques in the brain in Alzheimer’s disease (AD), is thought to be a critical alteration involved in oxidative damage to neurons. The project will use autopsied brain specimens from subjects with preclinical AD, patients with mild cognitive impairment and late stage AD, normal control subjects, a transgenic animal model of amyloidosis (APP/PS1 knock-in mice), and cultured neurons and glia to study Aβ-mediated RNA oxidation as an early event in AD that interferes with protein synthesis and neuron degeneration.. It will also investigate whether Aβ-mediated oxidation of specific proteins cause some of the pathological features of AD; elevated advanced glycation end products-ligand interaction with Aβ is an important process in the progression of AD; and Aβ activation of NADPH oxidase triggers a cascade linking increased free radicals to altered redox-based signaling and neurotoxic oxidative damage. The goal of the studies is to gain a better basic understanding of AD and identify novel therapeutic strategies which could lead to treatment of AD.
Other Sanders-Brown researchers for the study include: Mark Lovell, associate professor of chemistry, UK College of Arts and Sciences and Paul Murphy, assistant professor, and Harry LeVine, associate professor, Department of Molecular and Cellular Biochemistry, UK College of Medicine. Additional UK faculty include Daret St. Clair, professor, UK Graduate Center for Toxicology and Alan Butterfield, professor of chemistry, UK College of Arts and Sciences. Two researchers from the Pennington Biomedical Research Center at Louisiana State University also are participating. They are Anna Bruce-Keller, associate professor, and Jeff Keller, associate executive director for basic research.
The second study, previously funded for years 1-6 and now renewed for years 7-12, is “The Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADVISE).” It is funded for $1.3 million annually and is the largest AD prevention trial in the country.
The PREADVISE study is an important addition to the National Cancer Institute’s Selenium and Vitamin E Cancer Prevention Trial (SELECT). The purpose of PREADVISE is to determine if taking selenium and/or vitamin E supplements can prevent AD and other less common forms of dementia. Markesbery is the principal investigator and Dr. Frederick Schmitt, professor of neurology, UK College of Medicine, and Richard Kryscio, professor of statistics, UK College of Public Health, are the co-principal investigators. Currently more than 6,500 men have elected to take part in PREADVISE.
"The point in this study is to prevent Alzheimer's disease," said Markesbery. "We are studying men age 60 to 65 and older who are in good health at entry into the study."
In the PREADVISE study, some participants will receive vitamin E; some receive selenium; some receive a mix of both vitamin E and selenium; and others receive a placebo.