A Systems Biology Model of Alzheimer's Disease Incorporating Spatial-temporal Distribution of Beta Amyloid

摘要

Alzheimer's disease (AD) is one of the most devastating neurological disorders that affects the elderly. Pathological characteristics at the tissue and cell level include loss of synapses and neurons in the hippocampal and cortical regions, a significant inflammatory response, and deposition of the beta amyloid (Aβ) protein in brain parenchyma and within the basement membrane of cerebral blood vessels. These physical changes are believed to lead to gradual memory loss, changes in personality, depression and loss of control of voluntary muscle movement. Currently, 1 in 8 individuals over age 65 are affected by AD; this translates to over 5 million afflicted individuals in the US alone. Aβ has long been implicated as the main culprit in AD pathogenesis, though cholesterol, apolipoprotein E (apoE) and the low density lipoprotein-related receptor protein (LRP-1) are now also believed to play a role. In this paper, we describe a spatial-temporal mathematical model that has been developed to study the interactions between cholesterol, Aβ and LRP-1. Models for neuron survival, synapse formation and maintenance, and microglial motion have also been discussed. The paper concludes with a description of the proposed algorithm that we will use to simulate this complex system.