A Networkbased Investigation of the Mechanisms of Alzheimer's Disease: Use of systems biology tools to investigate Alzheimers, ,Used

A Networkbased Investigation of the Mechanisms of Alzheimer's Disease: Use of systems biology tools to investigate Alzheimers, ,Used

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We constructed two proteinprotein interaction networks from proteins involved in Alzheimers disease. Mapping gene expression data to one of the networks identified the MAPK/ERK pathway and clathrinmediated receptor endocytosis (CME) as key loci of altered gene expression in Alzheimers. The MAPK/ERK pathway is a critical component of learning and memory. CME affects production of the amyloidbeta peptide. We then used the network models plus additional data to identify potential noncoding SNPs that could affect gene expression. Three SNPs near the transcription start site of the transferrin gene had minor alleles frequencies that differed in Alzheimers patients versus controls. We then used systematic perturbations of the networks to model the effects of multiple interacting variants. The networks responded in an unexpected manner to multiple node or edge removals. Node and edges with lesser individual effects rose in importance in the networks as they were degraded. This suggests that Alzheimersassociated genes could be generated by a more random process than expected, and that proteins that initially appear unimportant may play a more significant role in pathogenesis.

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This warranty strictly does not cover damages that arose from negligence, misuse, wear and tear, or not in accordance with product instructions (dropping the product, etc.).

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