A Systems Biology Approach to Understanding Alzheimer’s Disease
Baras, John, S.
Date: April 30 - May 02, 2010
Alzheimer’s disease (AD) is the most prevalent form of dementia affecting the elderly. AD has devastating effects on the individual, leading to neuronal and synaptic loss, neuroinflammation, dysfunction of the blood-brain barrier and deposition of amyloid beta plaques in the brain parenchyma and cerebral blood vessels. Due to the inherent difficulty studying the many possible initiating factors of AD with in vivo models, we have chosen to approach this problem from a quantitative perspective initially to determine what key factors may initiate AD pathogenesis. We have developed a multi-scale systems biology model that describes the interactions between different components of the brain’s biological network at the tissue, cellular and transcriptional levels. Neurons have been modeled using a modified McCulloch-Pitts neural network that accounts for cell death and synapse loss due to varying amyloid beta and cholesterol levels. Microglia have been modeled in both the ramified and activated states using the Langevin equations of motion. The spatial-temporal distribution of beta amyloid has been modeled using the convection-reaction-diffusion equation with stochastic generation rates. Transport of beta amyloid by LRP-1 across the blood-brain barrier has also been modeled. Future generations of the model will take into account experimental results, as well as include models for plaque development in the basement membrane of cerebral blood vessels.