We describe the setup and optimization of a high-throughput screen (HTS) utilizing murine neuroblastoma N2a cells stably transfected with ApoE4 (N2a-E4) and a customized SirT1 AlphaLISA assay to screen the NIH Clinical Collection module from the UCLA compound library (http://www.mssr.ucla.edu/libraries.html), resulting in confirmation of A03’s SirT1-enhancing effects while not significantly affecting SirT2 levels. Here, SIRT1 is linked to neuroblastoma.