A Systems Biology Model Studying the Role of Cholesterol in Alzheimer’s Disease Progression

A simplified network describing the interactions between the cholesterol and beta amyloid (Aβ) synthesis pathways was generated using information available from literature and the KEGG database. A system of non-linear differential equations was developed and modeled using several different initial conditions. Rate constants were approximated using ratiometric data from the literature, or by fitting parameters to obtain a stable simulation within given biological constraints. Simulations demonstrated the importance of negative feedback control by cholesterol in the regulation of beta-amyloid levels. Additionally, the effect of reduced LRP-1 levels and oscillatory cholesterol generation was studied.