Kiminobu Sugaya, Ph.D.
University of Illinois at Chicago
Chicago, Illinois

2003 Investigator-Initiated Research Grant

The prime suspect in Alzheimer’s disease is the protein fragment beta-amyloid, clipped off the longer amyloid precursor protein (APP). Many investigational therapeutic strategies are aimed at finding ways to reduce beta-amyloid or prevent its cleavage from APP, but it is also critical to understand APP’s normal role in the body. There is evidence that APP may help guide the maturation of stem cells, “immature” cells that retain the capacity to develop into different types of mature cells. Small populations of stem cells remain active in the adult brain and these might be able to replace brain cells lost in Alzheimer’s disease.

Kiminobu Sugaya, PhD, and colleagues are studying whether APP plays dual roles of nudging mouse stem cells toward particular cell identities as well as influencing the migration of these cells from their “birth” zones to their adult homes. In particular, the researchers want to explore preliminary evidence that APP tends to nudge stem cells toward becoming glia, the supporting cells of the brain, rather than neurons, the cells that store, retrieve, and process information. The researchers will explore these questions both in laboratory cultures of brain stem cells and by introducing stem cells to the brains of different strains of mice that have been genetically engineered both to produce human APP and to lack APP completely. These mice will provide a “living laboratory” in which to explore APP’s impact on stem cells.