The Frost laboratory studies fundamental processes in cell biology that drive age-related neurodegenerative disorders. We employ a multi-system approach to rapidly identify, test, and validate hypotheses that are relevant to human aging and disease. Early discovery takes place in Drosophila, a model organism that is well-suited for investigating issues of causality in disease processes. To determine if our studies are relevant to vertebrates, we complement Drosophila work with comparative analyses in mouse brain tissue, iPSC-derived neurons, microglia, and astrocytes, and postmortem human brain tissue. We have recently completed a Phase IIa clinical trial (ART-AD) in patients with early Alzheimer's disease that is based on our discoveries.