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2017 Grants - van Weering
Seeding Disease: How Pathological Tau Meets Endogenous Tau
Jan van Weering, Ph.D.
VU University Medical Center
2017 Alzheimer’s Association Research Grant (AARG)
How does abnormal tau move between nerve cells in Alzheimer’s disease?
Tau protein normally functions to help support nerve cell structure and transport nutrients within the cell. In Alzheimer’s, tau can become abnormally modified and clump into tangles, one of the characteristic features of the disease. Recent evidence suggests that abnormal tau protein can move from one nerve cell to another, possibly contributing to the progression of brain changes associated with Alzheimer’s disease. In addition, scientists have shown that abnormally modified tau may move from damaged nerve cells into adjacent healthy nerve cells and trigger normal tau to form tangles. The mechanisms by which abnormal tau moves between nerve cells and induces the formation of tau tangles in healthy cells are not yet understood.
Jan van Weering Ph.D., and colleagues will use a special type of stem cell called “induced pluripotent stem cells” (iPSCs) to study how abnormal tau moves throughout the brain. iPSCs can be made from skin cells of adults and then “reprogrammed” to become other types of cells. For their studies, Dr. van Weering and team will transform the iPSCs into mature nerve cells that have the type of complex connections that would be seen in the human brain. They will then study how abnormal tau is released from one nerve cell and taken up by another. Their goal is to determine if tau may be floating free in the fluid between the cells, or packaged into small sacs called exosomes for transport. They hypothesize that the mechanism by which abnormal tau enters the healthy cell may influence its ability to trigger normal tau to clump. The scientists will use high resolution microscopy to visualize the interaction of abnormal and normal tau in the living nerve cells.
These studies could improve our understanding of how abnormal tau moves between nerve cells and triggers the formation of toxic tangles in healthy adjacent neurons. The results of this work could help identify new targets for the development of drugs that interfere with these processes to help slow or halt the progression of Alzheimer’s disease.