Autophagy is a fascinating new process that affects so many aspects of fundamental biology and human health and disease states including cancer, aging, metabolic disorders, immunology and inflammation (e.g. Crohn's disease), infection (HIV, tuberculosis), programmed cell death, and has also been implicated as playing a role in neurodegeneration (such as Alzheimer's disease). Autophagy literally means "self-digestion," and represents a process whereby cells capture portions of their own cytoplasm into specialized membranous structures termed autophagosomes where the captured material gets degraded. One could look upon this as a form of self-feeding--active particularly at times when a cell is subjected to starvation and there are no external sources of food. Our research is centered on the hypothesis that modulating autophagy could be utilized to slow the progression towards, and even prevent the inherent cognitive decline in, Alzheimer's disease and related disorders. We are using a technique known as high-throughput screening to identify pharmacological compounds, specifically FDA-approved drugs with known safety data, that can activate autophagy. We propose to quickly repurpose these drugs to target autophagy's ability to degrade intracellular debris against molecular aggregates (not just beta-amyloid) that we hypothesize cause inflammation in brain cells and lead to Alzheimer's disease. The goal of this proposal is to identify FDA-approved drugs that can activate autophagy for repurposing and off-label use as treatments for the prevention and cure of Alzheimer's disease.