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How does tau affect the communication between nerve cells in the brain, in Alzheimer’s and other brain diseases?
Che-Wei Chang
The J. David Gladstone Institutes
San Francisco, CA - United States
Background
A major challenge of Alzheimer’s is the inability to diagnose the underlying disease and to do so in its early stages. One of the early brain changes in Alzheimer’s involves the nerve cell network—the complex interconnections between nerve cells that are necessary for brain function. Studies have shown that in Alzheimer’s, the accumulation of an abnormal form of the protein tau in the brain interferes with the nerve cell network and impairs its function. Past studies have shown that in genetically-engineered Alzheimer’s like mouse models, reducing tau levels in the brain prevents these abnormal changes in the brain cell networks and therefore these animals do not experience the cognitive impairments. However, the mechanism by which this occurs is as yet unknown.
Research Plan
Dr. Che-Wei Chang will conduct a series of experiments to determine how tau interferes with the nerve cell network in the brain. Dr. Chang proposes that the tau protein specifically interferes with the activity of a special type of nerve cell (called the interneurons), responsible for relaying messages between other nerve cells in the brain. The researchers plan to test the effect of tau levels on activation of interneurons in genetically engineered Alzheimer’s-like mice. The researchers also plan to investigate if reducing tau levels could prevent cell death.
Finally, Dr. Chang will identify and analyze nerve cell communication biology that is known to be impacted by tau. To do this, the researchers will use nerve cells engineered from special kind of adult stem cells called induced pluripotent stem cells (iPSCs) - that can be reprogrammed into any cell type in the human body and examine the ability of tau to turn on or off specific proteins involved in these pathways.
Impact
By understanding the impact abnormal tau protein has on interneurons and the nerve cell networks, this work will help provide new information about this biology and lead to the development of new diagnostic tests to identify early-stage Alzheimer’s, as well as new therapies to slow the disease progression.
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