Studying the Role of ApoE in Alzheimer's Disease Pathogenesis Using a Systems Biology Model
C. R. Kyrtsos and J. S. Baras
Journal of Bioinformatics and Computational Biology (JBCB), Vol. 11, Issue 5, pp. 1342003.1-1342003.21, October 2013.
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 (A) plaques and neuro¯brillary 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 in°ammation at low to moderate levels. Simulations showed a late onset peak of A in the ApoE4 case that lead to localized neuron loss which could be ameliorated in part by application of short-term pro-in°ammatory mediators. The model that has been developed herein represents one of the ¯rst attempts to model AD from a systems approach to study physiologically relevant parameters that may prove useful to physicians in the future.
Keywords: A (beta amyloid protein); AD (Alzheimer's disease); APP (amyloid precursor protein); ApoE (apolipoprotein E); ApoE "2/3/4 (ApoE alleles); BACE (-secretase); BBB (blood–brain barrier); IL (interleukin); LTP (long term potentiation); NMDA (N-methy-Daspartate receptor); TNF (tumor necrosis factor); TREM2 (triggering receptor expressed on myeloid cells).