P1‐102: Building a Testable Mathematical Model for Alzheimer’s Disease Using Gene Expression Changes and Biochemical Systems Theory (BST)

Le résumé fourni par la source

Abnormal mitochondrial function has become recognized as a critical component in the pathogenesis of a variety of neurodegenerative diseases, including AD. We have recently found abnormal expression of several genes critical to mitochondrial energy production and biogenesis in AD brains. Using this subset of mitochondrial genes, we have begun to build a mathematical model of AD using Biochemical System Theory (BST). Through the development and application of appropriate differential equations, the flux of various metabolites and small molecules will be simulated and used to generate a testable model of mitochondrial involvement in AD pathogenesis. Human Mitochondrial Biogenesis and Energy Metabolism Plus RT Profiler PCR Arrays were used to assess expression of 168 mitochondrial function and energy genes in two control and four age- and gender-matched AD brains. These gene expression changes served as the starting point for MatLab-based mathematical analysis and BST dynamic computer simulations. Combining the data from our preliminary PCR array analysis with the mathematical modeling of these interactions using BST, we have generated a tentative working model shown here.

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