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2014 Grants - Rostagno
CAA, Mitochondrial Dysfunction and the Neurovascular Unit
Agueda Rostagno, Ph.D.
New York University School of Medicine
New York, New York
2014 Zenith Fellows Award
In addition to amyloid plaques within the brain, people who have Alzheimer’s disease also develop plaques in the blood vessels that supply the brain. This condition, known as cerebral amyloid angiopathy (CAA), impairs blood supply to the brain and damages the blood-brain barrier, allowing abnormal access of molecules from the blood into the brain. These consequences of CAA can worsen nerve cell damage and accelerate the progression of brain changes in Alzheimer’s disease.
Beta-amyloid, the primary component of amyloid plaques, exists in several forms in the brain. Before it forms plaques, beta-amyloid often exists in small clumps, known as oligomers. These oligomers are thought to be toxic to both nerve cells and endothelial cells, which line the inside surface of blood vessels.
Agueda Rostagno, Ph.D., and colleagues have been studying how beta-amyloid oligomers damage blood vessels in the brain and possibly lead to CAA. They have found evidence that oligomers damage mitochondria, specialized components of cells that provide energy to the cell. This damage may be more severe during conditions of low blood flow, when oxygen levels are low.
Dr. Rostagno and colleagues have proposed a series of experiments to study how low oxygen levels and beta-amyloid oligomers damage mitochondria and lead to dysfunction of the cells lining blood vessels in the brain. They will perform initial studies using cells growing in laboratory dishes and treated with a drug that protects mitochondria. The researchers will then extend their studies using mice that have been genetically modified to have an Alzheimer’s-like condition, which includes CAA. They will test whether protecting the mitochondria prevents damage to blood vessels in the brain when blood flow is reduced. These studies will improve our understanding of how CAA may contribute to the progression of Alzheimer’s disease.