Studying the role of Apoe in Alzheimer's disease pathogenesis using a systems biology model

C. Rose Kyrtsos and John S. Baras

To appear in the proceedings of the The 14th ACM Internation Symposium on Mobile and Ad Hoc Networking and Computing , Honolulu, Hawaii, USA, March 4-6, 2013.

Abstract

Alzheimer’s disease (AD) is a common form of dementia that is expected to increase in incidence in the next few decades. 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 using a graph theoretic approach has been developed and used to study the varying effects of variations in the ApoE allele present, as well as the effects 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.