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2005 Grant - Buckwalter

Altering TGF-Beta Signaling to Induce Neural Stem Cell Proliferation in Alzheimer's Disease

Marion S. Buckwalter, M.D., Ph.D.
Stanford University
Stanford, California

2005 New Investigator Research Grant

Because stem cells have the potential to turn into almost any cell type found in the body, they offer great hope for the treatment of a wide variety of diseases, including Alzheimer's disease. These cells might be used to help repair or support damaged nerve cells, for example, or they might be used to replace lost neurons.

In fact, in the human brain a type of stem cell called the neuronal precursor cell exists naturally. These cells can generate new neurons in some localized brain regions. However, both natural and trans-planted neural precursor cells grow poorly in older or inflamed brain tissue, potentially limiting their usefulness for treating Alzheimer's.

Marion Buckwalter, M.D., Ph.D., and colleagues will study how age and inflammation affect neuronal precursor cells. Previously, the researchers discovered that a protein called transforming growth factor-beta (TGF-beta), which accumulates as brains age, reduces the number of neuronal precursor cells in the brains of mice. This suggests that blocking the action of TGF-beta on precursor cells might increase their survival. To test this hypothesis, the researchers will engineer neuronal precursor cells so that they cannot succumb to the actions of TGF-beta and then transplant them into mice that have an Alzheimer-like disorder. The researchers will monitor the survival of the transplanted cells and determine if the mice show any improvement in symp-toms or if the number of neurons in the brain increases.

These studies may indicate whether transplanting stem cells that are unresponsive to TGF-beta may be a valid strategy to investigate as a treatment for people with Alzheimer's disease.