This project aims to determine how the brain proteome is remodeled in Alzheimer's disease (AD). AD is pathologically characterized by an accumulation of insoluble aggregates composed of Abeta peptides in the brain and is clinically characterized by progressive memory impairment. While the precise pathogenic mechanism(s) that drive AD remain unclear, synapse loss is a pathological hallmark and correlates with cognitive decline. Abeta peptides accumulate due in large part to perturbed protein degradation pathways, and increasing evidence shows that Abeta peptides impair multiple cellular pathways. To advance our understanding of these complex processes we have completed a comprehensive proteomic characterization of the three different AD mouse models before and after the onset of pathology.