In recent years, large amounts of genetic data have become available that reveal genetic associations with late-onset Alzheimer's disease. Many of the genes newly identified as important in Alzheimer's disease are involved in the immune system. One such gene encodes for a protein found on the surface of cells responsible for cleaning the brain of misfolded protein deposits that are a common feature of neurodegenerative diseases. Our goal is to develop drugs that can confer protection from neurodegeneration by stimulating these immune cells. We have solved the 3D atomic structure of this immune protein and used computational methods to identify compounds that bind to the protein and in doing so enhance the uptake of misfolded protein deposits by the brain immune cells. We will now develop these 'hit' compounds into a series of molecules with high potency, target specificity, and drug-like properties, so-called 'lead' molecules. We will do this by conducting a medicinal chemistry campaign, supported by established and new biological assays, to develop the hits into drug-like leads suitable for pre-clinical testing in Alzheimer's disease models. This work will involve an intensive, multi-disciplinary effort involving medicinal chemists, computational chemists, cell biologists, structural biologists and biophysicists with a strong track record in drug discovery and Alzheimer's research.