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2017 Grants - Iordanova
Relationship between Cerebral Amyloid Angiopathy and Neurovascular Deficits
Bistra Iordanova, Ph.D.
University of Pittsburgh
2017 Alzheimer’s Association Research Fellowship (AARF)
How does beta-amyloid accumulation in blood vessels relate to brain changes associated with Alzheimer’s disease?
Adequate blood flow to the brain is essential to delivering the oxygen and nutrients needed to maintain optimal function. Increasing evidence suggests that damage to the brain’s blood vessels may increase the risk of developing Alzheimer’s and related dementias. Reductions in blood flow could be connected to the build-up of beta-amyloid in the blood vessels – a condition known as cerebral amyloid angiopathy (CAA). Beta-amyloid is the protein fragment that can form plaques in the brain tissue, a hallmark of Alzheimer’s disease. More research is needed to determine how CAA may affect brain blood flow and nerve cell function in Alzheimer’s and related dementias.
Bistra Iordanova, Ph.D., and colleagues will compare mice that have amyloid plaques only in their brain tissue, to mice that have plaques in both their brain tissue and blood vessels (CAA). The mice that develop CAA carry a genetic variation (APOE-e4) associated with increased risk for Alzheimer’s. This experimental design allows the researchers to examine the impact of amyloid accumulation in different compartments of the brain. The researchers will use high-resolution brain imaging in living mice to determine how the development of CAA over time affects blood flow and nerve cell function. In addition, the team will determine if stimulating nerve cell activity can help improve blood flow and energy use (metabolism) in the targeted brain regions. Their preliminary results have found that stimulating the electrical activity of nerve cells can promote improved blood flow and oxygen to the area.
These studies will use newly developed live brain imaging techniques to improve our understanding of how amyloid accumulation in blood vessels relates to brain changes associated with Alzheimer’s disease. This work could help identify potential therapies that improve nerve cell function and brain blood flow as a way to slow or stop disease progression.