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2018 Alzheimer's Association Research Fellowship (AARF)

Role of extracellular vesicles in the propagation of synaptic dysfunction.

How do the toxic protein fragments associated with Alzheimer’s spread throughout the brain and affect nerve cells?

Ilaria Prada
CNR Neuroscience Institute - IN CNR
Pisa, Italy


Beta amyloid is a protein fragment that accumulates into amyloid plaques- one of the major hallmarks of Alzheimer’s. These plaques collect between nerve cells and are thought to impair brain cell function. As Alzheimer’s progresses it is not clear how beta-amyloid spreads to affect nerve cells in different regions of the brain. Microglia, the immune cells of the brain produce small enclosed capsules called “vesicles” that contain various proteins and other materials. These vesicles are released into the space between nerve cells and can travel along the surface of nerve cells. Dr. Ilaria Prada is examining the possibility that in Alzheimer’s, beta-amyloid spreads throughout the brain within these vesicles.

Research Plan

Dr. Prada and colleagues will use a combination of approaches to determine how vesicles containing beta-amyloid move along nerve cells grown in a laboratory dish and what the effect of these vesicles are on nerve cell function. They will use a tool called “optical tweezers”- that use light to manipulate very small objects- to physically place vesicles on nerve cells and then use a microscope to make time-lapse recordings of the vesicles as they move. They will also identify the molecules on the surface of nerve cells that make it possible for the vesicles to interact with them. Finally, they will examine the effect of beta-amyloid‒containing vesicles on the structure of the nerve cells.   


The results of this research will reveal whether microglial vesicles are responsible for how plaques develop within the brain in Alzheimer’s. Their findings may lead to the development of new therapeutic approaches that interfere with the activity of these vesicles to prevent the spread of beta-amyloid and slow the progression of Alzheimer’s.

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