Screen for Modulators of Abeta Toxicity in iPSC Neurons

Many past attempts to develop treatments for Alzheimer’s disease (AD) have focused on just one characteristic of the disease, the build up of a protein known as amyloid beta (Abeta, or Aβ), and have assumed that all patients will respond to new treatments in the same way. We have developed a series of laboratory tests that will enable us to look for ways to potentially correct a whole range of problems associated with Alzheimer’s disease. We also propose using cells derived from several patients in order to determine whether individual patients differ in how AD manifests and how they might respond to new treatments. The project combines a series of modern technologies and a deep understanding of AD that will, for the first time, enable us to answer some very practical questions about how we can make future AD treatments more effective.

The goal of our project is to identify potential new therapeutic paths for treating AD. We are doing this using multiple screening platforms. Unlike many other screens, we are using brain cells derived from different people. We use stem cells derived from living humans, and then, using induced pluripotent stem cell technology, we direct those cells to become the cells most affected by AD, namely, neurons and glia. We then look at multiple features of these cells in response to toxic proteins that are central to AD. By investigating cells from multiple people, we are investigating if and how different people’s brain cells respond to these toxic proteins. In addition, through screening strategies, we are looking for potential drugs that prevent toxic effects of these species. We then are investigating whether cells from different people respond differently to potential drug treatments. Once our study is complete, we hope that we will have identified novel therapeutic paths for Alzheimer’s disease, and identified which sets of patients are most likely to respond to those interventions.