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2024 Alzheimer's Association Research Fellowship (AARF)

Proteomics Profiling of Microglia for Cognitive Resilience in AD

Can specific types of the brain’s immune system promote protection of cognition, even with Alzheimer’s-related brain changes?

Yu Chen, Ph.D.
The Regents of the University of Michigan
Ann Arbor, MI - United States


Alzheimer’s is a progressive brain disease that impacts memory, learning, thinking, and behavior. Many older adults with Alzheimer’s progressively lose some cognitive capacities while retaining others. Some individuals are able to maintain their cognitive function, even in the presence of Alzheimer’s -related brain changes. These individuals are referred to as “cognitively resilient.” 

The underlying biology for this resilience is unclear, but some research suggests it may be linked to the brain’s immune system. The brain’s primary immune cell is called microglia. Microglia play a major role in helping to maintain healthy nerve cells. Individuals with Alzheimer’s typically experience brain inflammation caused by changes in the immune system, including increased activity of microglia. This increased activity may damage nearby nerve cells by swallowing them; this process is called phagocytosis. 

This study plans to learn if certain groups of microglia (meaning they have more or less of specific proteins present) are associated with cognitive resilience.

Research Plan

Dr. Chen and colleagues will use genetically engineered model systems to recreate Alzheimer’s-like brain changes. They will use an advanced computational technique known as “proteomics,” the study of the structure and functions of proteins made by cells. They will compare microglia from animal models with more “cognitive resilience” compared to animal models with more cognitive decline. Next, the research team will use the information from their proteomics experiments to investigate promising factors to determine if decreasing these factors changes cognitive resilience. 

Finally, the researchers will look at several different types of brain cells in the more cognitively resilient model compared to brain cells in the models with more cognitive changes. These brain cells will be compared to the same mice that do not experience cognitive resilience. The goal of this work is to determine if there are potential biological pathways that can be targeted as avenues to promote cognitive resilience.


If successful, this study may help researchers identify factors that offer potential treatment opportunities to improve cognition in individuals with Alzheimer’s.

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