The next challenge for proteomic research is gaining the cellular and temporal resolution to further define the causative role of cell-mediated dysfunction in AD pathogenesis. Cell type-specific proteomics in the human brain is currently in its infancy, primarily due to the inability to isolate live, pure cell populations from frozen brain and limited access to fresh postmortem tissue. The Seyfried Lab aims to extend localized proteomic approaches to mouse models of AD pathology for confirming the network architecture and investigating causal molecular changes during the cellular phase of disease. Furthermore, cell type-specific proteomics in disease and aging mouse models can serve to de-convolute complex human brain data and provide cellular-level resolution to peripheral biomarkers. This work will significantly enhance our understanding of the aging-dependent course of cell type-specific perturbations, thus allowing us to pinpoint opportunities for therapeutic intervention and enhance biomarker development.