Taking advantage of recent research progress, we propose to carry out a compound screen to find potential drugs to treat Alzheimer’s disease (AD). The screen will use a revolutionary 3-D stem cell model, recently developed by Drs. Rudy Tanzi and Doo Yeon Kim at Massachusetts General Hospital, which for the first time faithfully recapitulated major pathological hallmarks of AD in a dish. The screen also will use the previously developed neuronal image processing software packages, which are able to automatically and accurately assess the cell phenotype to evaluate the compound effect. Finally, we specifically will screen compounds that are known to be bioactive, including the compounds that already are used as drugs in clinics. Such a “drug repositioning” strategy will greatly reduce the cost of drug development, enable faster time to market and quickly translate the scientific discovery to patient bedside.