Presented at ICG12

Research area: neuroscience

Unexpected Early Proteomic Changes in Alzheimer's Disease Model Mice Synaptosomes

Created on 15th June 2017

K. Ball ; A. Pisconti ; K. Grounds ; W. Old ; M. Stowell

We have employed label-free quantitative proteomics of wild-type and Alzheimer's disease (AD) model mice synaptosomes to investigate proteomic changes occurring during AD progression as a prelude to analysis in humans. More than 4000 proteins were analyzed using multiple analysis tools and statistical criteria. Pathway enrichment identified numerous pathways consistent with the current AD knowledge base, including dysregulation of Glutamate Receptor Signaling, Synaptic Long Term Potentiation and Depression, Rho and Rac Signaling, Calcium Signaling, and Oxidative Phosphorylation and Mitochondrial Dysfunction. Additionally, the data demonstrate that a large number of changes occur in the proteome very early relative to the onset of both traditional disease markers such as amyloid accumulation, tau phosphorylation and cognitive dysfunction. These early changes include a number of dysregulated proteins that have novel associations with AD progression. These results reinforce the importance of mechanistic investigations in early disease progression long before the classical markers of Alzheimer's disease are observed.

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