(300 WORDS MAX) The number of people suffering from Alzheimer's disease (AD) is projected to grow from 5 to over 13 million by 2050 in the US alone, yet currently available drugs still only provide modest symptomatic relief at best. Moreover, these few drugs are not able to slow the progression of AD, or, critically, to protect the brain against the severe tissue damage that is part of the disease process. There thus remains an urgent need to develop innovative new drug strategies that intervene in the biochemical processes that underlie AD. In this context, this project seeks to optimize and evaluate new drug candidate molecules for treating AD based on a novel molecular target that we have recently discovered. This drug target, called protein disulfide isomerase, or PDI, is involved in pathological processes that are triggered by misfolded proteins like Abeta that are a central to the disease process in AD.