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2021 Alzheimer's Association Research Grant (AARG)

UNC-45A Uniquely Contributes to AD Pathology.

How might a protein that contributes to the stability of brain cells shape and structure contribute to brain changes in Alzheimer’s?

Martina Bazzaro, Ph.D.
University of Minnesota - Twin Cities
Minneapolis, MN - United States


Within brain cells, tube-shaped structures called microtubules are essential for maintaining cell shape, as well as the shape of connections between brain cells, known as synapses. In some neurodegenerative diseases, including Alzheimer’s, microtubules lose their integrity and become less stable. Studies have shown that using specific proteins to stabilize microtubules can lessen disease-related brain changes in genetically engineered Alzheimer’s-like mice. 

Dr. Martina Bazzaro and colleagues recently demonstrated that a protein called UNC-45A might cause microtubules to lose their integrity and become less stable.  Preliminary studies from the research team show that levels of UNC-45A are increased in multiple brain regions in individuals with mild cognitive impairment (MCI) and Alzheimer’s, compared to cognitively unimpaired individuals. These results suggest that UNC-45A may play a role in the development or progression of Alzheimer’s, though the underlying mechanisms are unknown.

Research Plan

To help understand the role of UNC-45A in Alzheimer’s, the researchers will study brain tissue from individuals who had Alzheimer’s as well as the brains of genetically engineered Alzheimer’s-like mice to determine the extent of UNC-45A activity across different brain regions. Next, the researchers will use advanced microscopic techniques to investigate how changes in the levels of UNC-45A changes the microtubule stability in brain cells grown in a laboratory dish. Finally, Dr. Bazzaro and colleagues will study whether levels of UNC-45A impacts the vulnerability of brain cells to biological changes seen in Alzheimer’s.


The results of this project may help shed light on biological brain changes associated with Alzheimer’s. The findings may potentially lead to new types of therapeutic interventions for Alzheimer’s and other dementias.

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