Modeling Alzheimer’s Disease Using A Systems Biology Approach
Baras, John, S.
Date: March 05 - March 09, 2011
Alzheimers disease (AD) is the most common form of dementia afflicting the elderly today and is believed to be caused by the buildup of the beta amyloid protein (Aß) within the brain and cerebral vasculature. Although a vast amount of knowledge exists, there is currently no definitive understanding of the initiating factor and subsequent pathogenesis, partially due to the difficulty in directly studying or manipulating the brain experimentally. To overcome this problem, we have developed a systems-level network that encompasses metabolic, lipidomic, and proteomic network topologies, taking into account known feedback and regulation mechanisms. By studying the interactions between the different networks computationally, we have identified several nodes which may be key for initiating a change from a healthy network state to a disease state. We have also performed in vivo experiments in APP/Swe/PS1 transgenic mice to study the effect of simvastatin, a cholesterol inhibitor and potent anti-inflammatory, on the expression levels of Aß, APP, LRP-1 and apoE. These experiments, in combination with our computational model, help to identify crucial feedback points and provide the first known attempt to model AD from a systems-level standpoint.