Rescuing cognitive processes—that is, one’s ability to remember things—is the ultimate goal of current and future therapeutics aiming to treat Alzheimer’s disease (AD). Here, we will investigate multiple factors that kill nerve cells leading to cognitive decline, and screen for preventive drugs previously approved by the U.S. Food and Drug Administration for the treatment of other diseases. This will allow us to fast-track an effective drug to clinical trials that will test whether the drug can protect cognition in people suffering from AD. We will study the effects of AD pathological proteins in human nerve cells in a cultured model and establish new methods to measure the efficacy of drugs to reduce the toxicity of pathological proteins. The significance of this project is demonstrated by screening downstream blockers of neurotoxicity after our success in identifying FDA-approved drugs and natural products for reducing AD pathological proteins.