Studying the Role of ApoE in Alzheimer's Disease Pathogenesis Using a Systems Biology Model

Alzheimer's disease (AD) is the most common form of dementia. Even with its well-known symptoms of memory loss and well-characterized pathology of beta-amyloid (Aβ) plaques and neurofibrillary tangles, the disease pathogenesis and initiating factors are still not well understood. To tackle this problem, a systems biology model has been developed and used to study the varying e®ects of variations in the ApoE allele present, as well as the e®ects of short term and periodic inflammation at low to moderate levels. Simulations showed a late onset peak of Aβ in the ApoE4 case that lead to localized neuron loss which could be ameliorated in part by application of short-term pro-inflammatory mediators. The model that has been developed herein represents one of the first attempts to model AD from a systems approach to study physiologically relevant parameters that may prove useful to physicians in the future.