Eric Schadt, et al. | Cell | 25 April 2013
Modeling the Complexity of Human Disease
Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer’s disease
Complex human diseases such as Alzheimer’s disease (AD) are not the result of defects in a single gene or the result of a single environmental factor, but rather are the result of many (even hundreds or thousands) genes interacting in complex ways with many environmental factors that result in the development, progression and severity of disease. Thus, just as weather systems, financial markets, and solar systems are modeled using advanced mathematical modeling techniques to understand the interactions among the many thousands of variables that define these complex systems, living systems must be similarly modeled to achieve an understanding of disease. Here we presented one of the first holistic molecular models for AD, elucidating the complexity of this disease at the molecular and cellular levels. By taking this objective, data driven approach to understanding AD, we were able to uncover that immune cells in the brain (microglia) were a key causal determinant for AD.