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2022 Alzheimer's Association Research Grant to Promote Diversity (AARG-D)

Microglia Regulation of Alzheimer’s Disease Pathology and Progression

Can a brain scan help visualize how immune cells in the brain can lead to increased risk of dementia?

Bahareh Ajami, Ph.D.
Oregon Health & Science University
Portland, OR - United States


The immune system is complex and serves to maintain our overall health. In the brain, the immune system specifically serves to maintain healthy nerve cells. Microglia are the primary immune cells of the brain, and they play a major role 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, which can damage nearby nerve cells. Recent studies have shown that overly active microglia tend to gather in areas of the brain susceptible to other dementia-related brain changes, such as beta-amyloid plaques and tau tangles, two hallmark brain changes associated with Alzheimer’s. These findings suggest microglia may play multiple roles in the development of brain disease.

In initial studies, Dr. Bahareh Ajami and colleagues used a novel brain scan technology called CODEX to analyze microglia in brain tissue from individuals who had Alzheimer’s. They found that this technique could identify different types of microglia in the brain samples, as well as how different types of microglia accumulate in different brain areas. 

Research Plan

Dr. Ajami and colleagues will now perform a larger study of microglia and Alzheimer’s with the CODEX brain scan method. First, they will scan fifty brain samples of individuals who had Alzheimer’s and examine how different types of microglia are arranged in two brain areas important for memory,  the cortex and hippocampus; both of these areas are also known to be more vulnerable to early Alzheimer’s brain changes. Next, they will determine how these different microglial types relate to plaques, tangles and other Alzheimer’s-related brain changes. The researchers will then use a sophisticated computer science technique called machine learning to study individual microglial cells in their scans, and determine which microglial groups may be linked to Alzheimer’s brain changes.    


This study could shed new light on the complex roles microglia play in brain diseases and open up the door to new avenues for therapy development.

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