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2019 Alzheimer's Association Research Fellowship to Promote Diversity (AARF-D)

Astrocytes as a New Cellular Player in Tau-Induced Neurotoxicity in Alzheimer's Disease

How might support cells in the brain called astrocytes contribute to the transportation of tau in the brain in Alzheimer’s?

Pablo Cisternas, Ph.D.
Indiana University
Bloomington, IN - United States


One of the hallmark features of Alzheimer’s is the accumulation of protein fragments in the brain- Beta-amyloid protein fragments can accumulate into plaques that could damage nerve cells. Studies show that plaques could give rise to accumulation of another protein called tau. The brain cell’s nutrient and energy transport system is organized in parallel strands like railroad tracks. These tracks allow nutrients to travel across the cell, delivering key materials to the cells, providing them with energy and keeping them healthy. The tau protein helps keep these tracks straight. However, in Alzheimer’s and other brain diseases like frontotemporal dementia and Pick’s disease the shape of tau protein becomes modified and this could contribute to tau tangles (a hallmark of these diseases) and subsequent nerve cell damage.
Astrocytes are the most numerous cell types in the brain and play an important role in supporting nerve cell function. Studies show in the presence of beta-amyloid, astrocytes could make modified tau. Dr. Pablo Cisternas believes that because of the close relationship between astrocytes and nerve cells, tau made by astrocytes could be transported between nerve cells in the brain and may worsen Alzheimer’s symptoms.

Research Plan

Dr. Cisternas’ team will examine how beta-amyloid causes astrocytes to make modified tau in Alzheimer’s, and how it is transported in the brain. Their goal is to better understand the relationship between beta-amyloid and tau movement in the brain, centering on the role of astrocytes.
In the first part of the study, the researchers will grow nerve cells and astrocytes in laboratory dishes and expose the cells to beta-amyloid. They will measure cell death and determine how tau made by astrocytes moves from cell to cell. They will also determine if preventing astrocytes from making tau can preserve cell functions in the model. The researchers will also apply tau made by astrocytes, to nerve cells in a laboratory dish to determine seeding— a process by which in individual nerve cells in the brain, tau protein is recruited to form tangles —capacity of this tau. Past studies link fast tau seeding to more rapid impairment of memory and cognition.

Finally, Dr. Cisternas’ team will study the role of tau made by astrocytes in genetically-engineered Alzheimer’s-like mice. The researchers will study how tau made by astrocytes is transported in the brains of the mice. Dr. Cisternas believes that this process may worsen brain changes and behavioral symptoms associated with Alzheimer’s.



If successful, this study could identify a new player in the transport of modified tau throughout the brain in Alzheimer’s. An understanding of the biological mechanisms by which tau is transported in the brain may help identify or better develop therapeutic targets.

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