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2022 Alzheimer's Association Research Grant (AARG)

Single-cell analysis of neutrophil subpopulations Alzheimer’s disease mice

How do immune cells contribute to Alzheimer’s disease progression?

Oliver Bracko, Ph.D.
University of Miami
Coral Gables, FL - United States


As individuals age, blood vessels can become damaged. This may impact blood flow to the brain and other parts of the body. Studies show that blood vessel damage may also impact an individual’s risk for many brain diseases, including Alzheimer’s. In initial studies with mice genetically-engineered to develop Alzheimer’s-like brain changes, Dr. Oliver Bracko and colleagues found that immune cells called neutrophils were linked to loss of blood flow in the brain. Neutrophils normally help heal damaged brain tissue and fight infections by releasing substances called neutrophil extracellular traps (NETs) in the brain. In these models, neutrophils appeared to slow brain blood flow by attaching themselves to the inner lining of capillaries (small blood vessels) in the brain. Dr. Bracko’s team also observed that by reducing neutrophil activity, they could improve blood flow and short term memory in other Alzheimer’s-like mice.

Research Plan

The investigators will now conduct a larger study to better clarify the role of neutrophils in blood flow loss and cognitive decline. First, they will use sophisticated brain scan techniques to examine how neutrophils interact with blood vessels in the brains of Alzheimer’s-like mice. They will also measure levels of blood vessel damage produced by the neutrophils – damage such as inflammation and blood flow decline. Then, Dr. Bracko and colleagues will study the individual neurotrophic cell patterns of what genes are turned “on” and “off” in a given cell in response to their environment or disease state. Dr. Bracko’s analysis will help identify certain groups of neutrophils that are most likely to impact brain blood flow function and promote brain disease.    


This study will shed new light on the role of neutrophils in Alzheimer’s and other dementias. This may open new paths for new methods for early and accurate diagnosis and therapy approaches.

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