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2010 Grants - Scholtzova
Mechanisms of Action of Innate Immunity Stimulation with CpG ODN on CAA
Henrieta Scholtzova, M.D., Ph.D.
New York University School of Medicine
New York, New York
2010 New Investigator Research Grant
The innate immune system is an ancient self-defense mechanism for fighting off microbial invaders. It acts as a one-size-fits-all system that attacks any foreign matter in exactly the same manner. One of the innate immune system's key components is the macrophage, an immune cell that can engulf and degrade foreign matter.
In recent studies with mice engineered to develop Alzheimer-like symptoms, Henrieta Scholtzova, M.D., Ph.D., and colleagues tested an amyloid-reducing compound called CpG ODN. They found that CpG ODN stimulated the rodents' innate immune system macrophages to destroy beta-amyloid in the brain and blood vessels. These amyloid reductions, in turn, improved dementia-related behavioral problems in the mice. Moreover, the treatment was able to clear vascular beta-amyloid, also known as cerebral amyloid angiopathy (CAA), without causing the brain hemorrhages often associated with this kind of treatment.
For their proposed grant, Dr. Scholtzova and colleagues will try to confirm and expand these promising results. They will look for biological mechanisms that explain how the activation of macrophages by CpG ODN safely regulates vascular and brain beta-amyloid levels. To accomplish their goals, the researchers will use cells gathered from Alzheimer-like mice.
The results of this study could shed new light on the role of the innate immune system in Alzheimer's disease. The effort could also lead to safe, effective immunization therapies for Alzheimer's.