2005 Investigator-Initiated Research Grant

Growing evidence suggests that the production of new nerve cells, or neurogenesis, is important for normal brain functions such as learning, memory, and mood control—all of which are adversely affected in Alzheimer’s disease. There is also evidence in studies with cultured cells suggesting that amyloid plaques, a key feature of Alzheimer’s, may impair neurogenesis. For technical reasons, researchers have not been able to determine whether neurogenesis is, indeed, impaired in the Alzheimer brain.

Recent studies by Yi E. Sun, Ph.D., and other investigators have identified a transcription factor, a kind of molecular switch, called neuroD, which turns on genes involved in neurogenesis in adult mice. A measure of neuroD may, therefore, function as an indirect gauge of neurogenesis.

In the current investigation, Dr. Sun and colleagues are engineering a compound that binds to neuroD and functions as a kind label that will enable them to quantify neurogenesis in the adult mouse brain. The intent is develop a labeling tool that can eventually be adapted for examination of autopsied human brains or brain imaging methods to determine (1) whether neuroD can function as marker of neurogenesis in the human brain and (2) whether neurogenesis is impaired in Alzheimer’s disease.

In a related set of experiments, Dr. Sun’s group will crossbreed two lines of mice: (1) mice genetically altered to develop an Alzheimer-like disorder and (2) mice that can have their neurogenesis function manipulated with the use of a specific drug. In studies with the new mice, the researchers will examine (1) whether Alzheimer-like symptoms in mice are exacerbated in the absence of neurogenesis and (2) whether enhancing neurogenesis has any beneficial effect on Alzheimer-like symptoms.

The findings may shed light on the impact of Alzheimer’s disease on neurogenesis and may provide investigators with tools to study the issue in humans.