John S. Baras


Modeling Alzheimer's Disease Using A Systems Biology Approach

C. Kyrtsos and J. S. Baras

Proceedings of the 2011 Biophysical Society,  Baltimore, MD, March 5-9, 2011.


Alzheimer’s 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.


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