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2009 Grants - Liu
Chronic Cerebral Hypoperfusion and Alzheimer's Disease Pathogenesis
Li Liu, Ph.D.
New York, New York
2009 New Investigator Research Grant
Many of the risk factors for late-onset Alzheimer's disease are related to the health of the vascular system. When these risk factors are present, they can lead to low blood flow (hypoperfusion) in the brain. Although hypoperfusion of the brain is often associated with Alzheimer's disease, it has not been established as a cause of the disease.
Li Liu, Ph.D. and colleagues have proposed to study whether brain hypoperfusion causes the development of Alzheimer pathology. For these studies, the researchers will use a strain of rats that have been genetically altered to exhibit Alzheimer-like pathology. They will determine if reducing brain blood flow leads to the development of amyloid plaques and neurofibrillary tangles, two hallmark features of Alzheimer pathology. Dr. Liu's team will also study brain hypoperfusion in older rats to determine if it causes worsening of established disease.
To begin understanding the molecular mechanisms that mediate the effects of hypoperfusion, the researchers will use biochemical techniques to measure the activity of enzymes known to be involved in the production of beta-amyloid, the protein fragment that aggregates into amyloid plaque. These studies will test an important concept regarding the factors that initiate the development of Alzheimer's disease and that promote disease progression.