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
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Conference : 40th Annual Meeting Neuroscience 2010
Date: November 13 - November 17, 2010

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 ratiometric data. 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. Future work will look further at the role of the negative feedback loop that cholesterol provides both in silico as well as in vivo with an APP/PS1 transgenic mouse model.

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