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2019 Alzheimer's Association Research Grant (AARG)

Rejuvenating Microglia in a Mouse Model of Alzheimer’s Disease

What impact do replacing old immune system cells in the brain with young immune cells have on brain health and Alzheimer’s disease?

Anna Majewska, Ph.D.
University of Rochester
Rochester, NY - United States


Alzheimer’s is characterized in part by the accumulation of protein fragment beta-amyloid and an abnormal form of the tau protein. Specialized immune cells that live in the brain called microglia stimulate response to remove beta-amyloid and abnormal tau.  In Alzheimer’s disease, however, microglia become abnormally activated, which may hinder them from properly clearing beta-amyloid and tau. Overactive microglia can lead to toxic inflammation within the brain and, ultimately lead to nerve cell death. While it is unclear exactly why microglia becomes dysfunctional in Alzheimer’s, past studies suggest that microglia become weakened in the aging Alzheimer’s brain. These “aged” microglia lose their ability to carry out helpful activities.

Research Plan

Dr. Anna Majewska and colleagues will use genetically engineered Alzheimer’s-like mice to test whether replacing “older,” weakened microglia with newly-born microglia can improve the health and function of the mice brains. The researchers will use a novel compound that will eliminate aged microglia from the animals’ brains and allow the creation of new and young microglia. Dr. Majewska will then use brain scans and other methods to test how well the newly-born microglia clear beta-amyloid plaques from the mouse brains and prevent harmful brain inflammation. The researchers will also assess whether the newly-born microglia reduces changes in cognition seen in these Alzheimer’s-like mice.


The study results could improve our understanding of how the immune system becomes damaged in Alzheimer’s disease. The results could also shed light on novel therapeutic strategies for slowing or reversing Alzheimer’s progression.

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