By exposing genes associated with disease, genomic studies provide hundreds of starting points that should lead to druggable processes. However, our ability to systematically translate these genomic findings into biological pathways remains limited. Here, we combine rapid loss-of-function mutagenesis of Alzheimer's risk genes and behavioural pharmacology in zebrafish to predict disrupted processes and candidate therapeutics. FramebyFrame, our expanded package for the analysis of larval behaviours, revealed that decreased night-time sleep was common to F0 knockouts of all four late-onset Alzheimer's risk genes tested. We developed an online tool, ZOLTAR, which compares any behavioural fingerprint to a library of fingerprints from larvae treated with 3677 compounds. ZOLTAR successfully predicted that