Alzheimer's Disease Research
Paul H. Axelsen, M.D.
University of Pennsylvania
Philadelphia , PA, United States
Title: Oxidative Lipid Degradation in Alzheimer's Disease
Non-Technical Title: Oxidative Stress in Alzheimer's Disease
Duration: July 1, 2011 - December 31, 2013
Award Type: Standard
Award Amount: $250,000
Oxidative stress will be examined in animal models of Alzheimer's disease using novel radiolabeled compounds that are designed to reveal how the proteins that accumulate in Alzheimer's disease are induced to form fibrils and plaques.
We all need oxygen to survive, but oxygen can react with chemicals in the body to create harmful byproducts and “oxidative stress.” Dr. Paul Axelsen and colleagues will study the role of oxidative stress in Alzheimer's disease. They will attempt to determine how oxidative stress causes chemical changes in dietary fats (including omega‐3 and omega‐6) that can damage brain amyloid proteins. These researchers will use special tracers on the fats to detect the changes in dietary fats and in the amyloid proteins of mouse models of Alzheimer's disease and oxidative stress. The results from this study may give ideas on how to fight oxidative stress in the human brain.
This project involves the biosynthesis of isotope-labeled fatty acids and their injection into aged transgenic mice to understand how these materials are metabolized. Both of these procedures - biosynthesis and aging a mouse colony - have long lead times (over a year), but are well underway at this point. When ready, however, we expect them to provide unprecedented and detailed insight into the root causes of Alzheimer’s disease.
Dr. Axelsen underwent research training in biophysics at the University of Washington and at the Mayo Clinic. He received an L.P. Markey Biomedical Scholar Award and joined the Mayo staff in 1989. While a short-term visiting scholar at the Weizmann Institute, he was recruited to Penn in 1993. Axelsen's clinical experience has included overseas work in Papua New Guinea and Bangalore India, various emergency room and infectious diseases staff positions in Minnesota, and the Immunodeficiency Program at Penn as a clinical HIV/AIDS specialist. Research highlights from the Axelsen laboratory include more than 80 publications in the fields of pharmacology, computational chemistry, and experimental biophysics.