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

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

Title : A Systems Biology Model Studying the Role of Cholesterol in Alzheimer's Disease Pathogenesis
Authors :
Baras, John S.
Kyrtsos, C Rose
Conference : Proceedings of the 2011 Biophysical Society
Date: March 05 - March 09, 2011

A simplified network describing the interactions between the cholesterol and beta amyloid (Aβ) synthesis pathways was generated using information available from the KEGG database and literature. A system of ordinary differential equations was developed and modeled using Matlab. Rate constants and molecular concentrations were approximated using basic parameter estimation. Initial simulations demonstrated the importance of negative feedback control by cholesterol in the regulation of beta amyloid levels. Eliminating negative feedback by beta amyloid on cholesterol, as well as decreasing the initial levels of cholesterol or Aβ, led to no changes in the steady state levels of molecules studied. The model was then adapted to include compartmentalization of cholesterol and ApoE into neuronal, astrocytic and free ApoE. This adapted model was used to study the effect of decreasing ApoE, decreased neuronal cholesterol, decreased acetyl CoA, as well as decreased LRP-1 expression. Future work will continue to expand on the model to include further compartmentalization, where applicable, as well as the possible effect of statin treatments on the concentration levels of key proteins (Aβ, ApoE, LRP-1). Future models will also use a Monte Carlo simulation method to study the effect of noise on such a system

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