Our goal is to identify therapeutic targets for Alzheimer’s disease and other tau-related neurodegenerative diseases. We model relevant cellular disease processes in neurons derived from human induced pluripotent stem cells (iPSCs) with disease mutations. CRISPR editing enables us to introduce or correct disease mutations, creating neurons that differ only in the disease gene. We combine these cellular models of disease with our CRISPR-interference based genetic screening approach to uncover mechanisms underlying disease processes, and to identify therapeutic strategies that can correct disease-associated cellular defects.