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2015 Grants - Ashe
Toward Understanding Mechanisms of Tau Neurotoxicity in the Mammalian Brain
Karen Hsiao Ashe, M.D., Ph.D.
University of Minnesota — Twin Cities
2015 Zenith Fellows Award
Tau is a protein at the focus of research into Alzheimer’s disease. In healthy nerve cells, tau helps to maintain cell structure and transport nutrients throughout the cell. In Alzheimer’s disease and other neurodegenerative diseases, however, tau becomes abnormally modified and can accumulate into neurofibrillary tangles, which disrupt cell function and can be toxic to nerve cells.
The mechanisms of how tau is toxic to nerve cells are not well understood. Many studies have explored this question in simple animal models (such as worms) and in nerve cells growing in laboratory dishes. But the mechanisms of tau toxicity in those models may not represent the mechanisms in nerve cells growing in the brains of mammals.
Karen Hsiao Ashe, M.D., Ph.D., and colleagues are working with other scientists to use a newly developed method for measuring modifications of tau in the living brain. They will use this novel method to assess how different modifications of tau lead to toxic effects in nerve cells. The experiments will be performed in mice genetically altered to have different variations of tau. These studies will provide critical information on how tau causes nerve cell damage in the living brain, and may suggest new ways to prevent tau toxicity and slow the progression of Alzheimer’s disease and other neurodegenerative diseases.