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2015 Grants - Despa
Role of Oligomerized Amylin in Vascular Injury and Alzheimer’s Disease
Florin Despa, Ph.D.
University of Kentucky
2015 Role of Vascular Metabolic Factors in the Pathogenesis of Alzheimer’s Disease and Related Dementia Grant
Do high levels of amylin in the blood contribute to brain blood vessel damage and other brain changes associated with Alzheimer’s disease?
One of the strongest risk factors for Alzheimer’s disease is diabetes but the underlying mechanisms of this link remain unclear. Diabetes is also a strong risk factor for other types of brain diseases, especially those involving damage to the blood vessels. Damage to the blood vessels in the brain can lead to stroke or vascular dementia, a condition related to Alzheimer’s disease.
Amylin is a protein-like hormone secreted by the pancreas. It works along with insulin to help the body control blood sugar levels. In people with obesity or diabetes, amylin levels in the blood can be unusually high. Recently, it has been shown that amylin can accumulate into toxic clumps in brain blood vessels, possibly contributing to brain damage and cognitive problems. In addition, amylin can also clump together with beta-amyloid, a protein fragment known to play a role Alzheimer’s disease. Beta-amyloid forms the plaques that are hallmark of Alzheimer’s disease in the brain. The relationship between amylin and beta-amyloid may provide a mechanism for how obesity and diabetes increase the risk for Alzheimer’s.
Florin Despa, Ph.D., and colleagues have proposed a series of experiments to explore if amylin accumulation in the brain is associated with blood vessel injury and dementia. The researchers will study samples of brain tissue, blood and cerebrospinal fluid (the fluid that surrounds nerve cells in the brain) to measure amylin levels in individuals that had (1) diabetes+dementia, (2) only dementia or (3) only diabetes. They will determine how amylin levels in the blood relate to amylin build-up in the brain. The researchers will also study mice that have been genetically-engineered to develop amylin deposits in their brain blood vessels. They will determine if this leads to Alzheimer’s-like brain changes and memory problems in the mice.
This research may help explain how risk factors for Alzheimer’s such as obesity and diabetes affect the health of blood vessels in the brain. This work could also shed new light on the relationship between amylin and beta-amyloid in the brain. Most importantly, these findings may lead to the development of treatments to prevent amylin accumulation and brain injury in people at risk for Alzheimer’s disease.