Our lab has historically been involved in defining the underlying neurodegenerative mechanisms in Alzheimer’s disease and in the search for therapeutic agents. We discovered the phenomenon of amyloid neurotoxicity and identified the first anti-amyloid aggregation agents. Our present approach, however, seeks to mimic mechanisms of successful aging in humans by increasing our understanding of how some people can live long lives without cognitive problems. The goal is to recapitulate the molecular mechanisms of successful aging with therapeutic agents. To accomplish this goal, we perform genomic screens in worms and neuronal cells in culture, and then investigate potential therapeutic targets in animal models and in the human brain.