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2017 Grants - Vidal
In vivo Analysis of Cell-Type-Specific Expression of Tau and Tau Spreading
Ruben Vidal, Ph.D.
2017 Zenith Fellows Award Program
What types of cells are involved in the formation and spread of abnormal tau protein in the brain during Alzheimer’s disease?
Tau is a protein that normally helps to maintain nerve cell structure and transport nutrients throughout the cell. In Alzheimer’s disease, tau becomes abnormally modified and can form tau tangles in the brain, a hallmark of the disease. Recent evidence suggests that abnormal tau protein can spread from one nerve cell to the next, possibly contributing to the progression of brain changes associated with Alzheimer’s disease. However, the mechanisms that underlie the accumulation and movement of abnormal tau in the brain are not well understood.
Ruben Vidal, Ph.D. and colleagues will conduct a series of experiments to determine which cell types in the brain may be involved in the spread of abnormal tau. They will use mice genetically engineered to lack tau in either nerve cells, or support cells in the brain called astrocytes. The research team will then administer abnormal human tau protein into the brains of the mice and determine if “deleting” tau from the nerve cells, versus astrocytes, prevents the toxic tau from spreading. These results will help identify which cell types are important in the propagation of the disease. The mice will be followed for several months to measure the extent of tau spreading, brain inflammation and nerve cell loss. The mice will also be tested for changes in memory function.
The results of this study could identify which types of brain cells may contribute to the accumulation and spread of abnormal tau throughout the brain in Alzheimer’s and other neurodegenerative diseases, such as frontotemporal dementia or traumatic brain injury. Importantly, these studies could also identity new targets for drug treatments aimed at blocking the spread of abnormal tau protein to help slow or prevent disease progression.