Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by progressive cognitive decline and dementia. Recently, genetic studies have identified and validated several genes, which point to the immune system being involved in susceptibility to AD and therefore should to be explored for therapeutic intervention. It has now become clear that the immune system plays many different roles in the brain during health and disease; one of these functions is the removal of aggregated protein and dying cells. While the importance of these cells is now at the forefront of identifying new therapeutic routes for neurodegenerative diseases, the question of whether to activate or suppress these cells maybe an oversimplification. We hypothesis that increasing the ability of these cells to clear protein aggregates and dead cells could be beneficial, but it should done in a way that limits a pro-inflammatory response that could be detrimental and diminish the gains made by increasing the clearance ability. Herein, we propose to identify small molecules from a library of biologically active compounds, which modulate clearence ability in immune cells. Small molecule hits will then be evaluated for production of a panel of proteins. Since it has been demonstrated that immune cells from patients with AD are less capable of clearance, we will evaluate the ability of these small molecules to modulate these functions in cells from both AD subjects and age-matched controls. We anticipate that this study will provide two avenues for therapeutic advancement in AD: 1) it will identify drugs which could be repurposed for AD and 2) it will help elucidate putative pathways and additional targets mediating AD risk, against which future drug discovery efforts could be developed.