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- Title
Computational prediction of changes in metabolic reaction rates for Alzheimer's disease in the context of different brain regions.
- Authors
Konuk, Hatice Büşra; Çakır, Tunahan
- Abstract
Objective: Alzheimer's disease (AD) is a type of dementia that causes impairment in memory, reasoning and thinking. Incidence and progression of AD are correlated with metabolic dysfunction. Our aim is to predict changes in the rates of metabolic reactions computationally for hippocampus, entorhinal cortex, superior frontal gyrus, medial temporal gyrus and primary visual cortex. The computational approach integrates measured rates with the changes in gene expression levels of AD patients. Methods: A basic metabolic network model that includes 71 reactions of central carbon metabolism was used to estimate metabolic reaction rates for five different regions of healthy brain by using a computational approach that combines steady state balancing around metabolites with optimization. Metabolic rates of AD patients were then predicted based on the same model by using the gene expression profiles of AD patients retrieved from a public transcriptome database (Gene Expression Omnibus). Results: Metabolic reaction rates of healthy subjects and AD patients were predicted, and compared with each other to understand metabolic dysfunction in the five different brain regions. Reaction rates for healthy brain were found to be similar to literature, there are some differences among various regions, though. Comparison of reaction rates of AD patients demonstrate that hippocampus and entorhinal cortex are the most affected and primary visual cortex is the least affected region. Glucose and oxygen uptake rates are predicted to be significantly decreased in the mostly affected regions. Moreover, predicted decrease in ATP production rate and increase in the GABA shunt activity in AD patients are found to be in accordance with literature. Conclusion: Mapping gene expression profiles on the metabolic model computationally gave us crucial perspective about changes in the metabolic pathways of different brain regions in AD. A comprehensive brain specific metabolic network model and different mapping algorithms are going to be performed to obtain more reliable results.
- Subjects
ALZHEIMER'S disease; AMYLOID beta-protein; AMYLOID beta-protein precursor; GENE expression profiling; ENTORHINAL cortex; VISUAL cortex; BRAIN
- Publication
Anatomy: International Journal of Experimental & Clinical Anatomy, 2019, Vol 13, Issue S1, pS65
- ISSN
1307-8798
- Publication type
Article