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2008 Grants - Cribbs
Reducing the Risk of Cerebral Vascular Adverse Events in Alzheimer's Disease
David H. Cribbs, Ph.D.
The University of California, Irvine
2008 Investigator-Initiated Research Grant
A hallmark of Alzheimer's disease is the build-up of beta-amyloid, a protein fragment. Yet this fragment is also found in the brains of people without the disease. One possible reason for why beta-amyloid does not always cause Alzheimer's may be that problems with blood circulation and inflammation in the brain must also exist for the disease to progress. Scientists have observed that excess beta-amyloid reduces the ability of the brain's blood vessels to regulate blood flow. This dysregulation deprives the brain of the sufficient oxygen and nutrients it needs to function properly. Excess beta-amyloid has also been shown to cause inflammation in the brain's blood vessel system.
To date, scientists know little about how beta-amyloid may be involved in vascular diseases of the brain. Many researchers believe that such knowledge could be advanced by developing and testing more effective animal models. Ideal models should develop amyloid-related blood vessel disorders that closely resemble those found in humans.
To address this problem, David H. Cribbs, Ph.D., and colleagues have identified two promising types of genetically engineered mice. They plan to use their animals to test the ability of certain drugs to reduce beta-amyloid levels and prevent amyloid-induced blood vessel damage. In a related effort with the mice, researchers will administer the same drugs along with beta-amyloid "vaccines," or modified beta-amyloid molecules intended to induce the immune system to develop an amyloid antibody. Such vaccines have been shown to cause brain inflammation in human clinical trials. Dr. Cribbs' team hopes that the drugs will prevent the vaccines from causing inflammation in its mice.
The findings of this study could identify novel, safe Alzheimer therapies for testing in future human clinical trials.