2004 New Investigator Research Grant

Many cases of the rare inherited form of Alzheimer’s disease can be linked to mutations in the PS1 gene, the biological blueprint for the presenilin-1 protein. Research about the normal and disease-related functions of this protein have provided valuable insight into cellular events in Alzheimer’s.

Previous research has shown that one function of presenilin-1 may be activating a protein called PI3K. This protein regulates several signaling pathways, or molecular chains of command, that control important cell activities. In previous studies, Apostolia Baki, Ph.D., and colleagues found that presenilin-activated PI3K regulates a pathway that promotes cell survival and another pathway that suppresses chemical changes in a protein called tau.

The researchers have hypothesized that Alzheimer-related presenilin-1 fails to activate PI3K. This disruption in normal PI3K function may, in turn, allow the development of some key features of Alzheimer’s disease: (1) activation of cellular systems that cause a cell to self destruct and (2) chemical changes in tau that lead to the formation of neurofibrillary tangles, abnormal structures which accumulate inside brain cells and are associated with cellular damage.

In this study, the investigators will further characterize the role of nonmutated and mutated PS1 on the activation of PI3K in cell cultures. This work may identify key steps in complex molecular interactions that are valid targets for new drug development.