John A. Oates Jr., M.D.
Oates receives international award for Alzheimer’s research
John A. Oates Jr., M.D., Thomas F. Frist Sr. Professor of Medicine and professor of Pharmacology, has received a three-year, $500,000 award to study the link between the cyclooxygenase (COX) enzymes and Alzheimer’s disease.
The American Health Assistance Foundation’s Alzheimer’s Disease Research program presented its first international award to Oates on Monday during the Ninth International Conference on Alzheimer’s Disease and Related Disorders in Philadelphia.
“This is going to give a great boost to Alzheimer’s disease research at Vanderbilt,” Oates said in a phone interview. “The award reflects the strength of the research being conducted by many of my colleagues (here).”
Oates, who has made major contributions to current understanding of the COX enzyme pathways, is the principal investigator of the award.
Co-investigators are Olivier Boutaud, Ph.D., research assistant professor of Pharmacology at Vanderbilt, Katrin Andreasson, M.D., assistant professor of Neurology and Neuroscience at the Johns Hopkins School of Medicine, and Venkataraman Amarnath, Ph.D., research associate professor of Pathology at Vanderbilt.
The Vanderbilt researchers previously have reported that the COX enzyme pathway can lead to production of highly reactive molecular compounds called levuglandins. These compounds can accelerate the formation of aggregates of beta-amyloid protein that are toxic to nerve cells.
The finding may help explain how the use of non-steroidal anti-inflammatory drugs, which inhibit the COX enzymes, seems to reduce the risk of developing Alzheimer’s disease.
At this week’s conference, Oates and his colleagues reported that they found a twelevefold increase in the level of “adducts,” irreversible attachments of levuglandins to proteins, in the brains of patients who had Alzheimer’s disease compared to age-matched control brains.
“The level of this COX-derived lipid modification of brain proteins is highly correlated with the … severity of the Alzheimer’s disease and provides tangible new evidence for participation of COX activity in the disease,” they said.
The researchers are developing a series of potent “scavengers,” compounds capable of modifying levuglandins so that they no longer can form neurologically toxic adducts.