Alzheimer's disease (AD) is the most common fatal nerve degeneration disorder, afflicting ~27 million people worldwide. Beyond minor symptomatic relief, there are no effective treatments. A major risk factor for AD is aging. Consequently, as life expectancy increases and population demographics shift toward older age groups, AD is projected to increase ~4-fold by 2050, and threatens to devour our social and economic resources. This threat is unacceptable and must be eliminated. A defining feature of AD is the presence of clumps of protein in the brain. Small molecule drugs are urgently needed to safely dissolve these clumps. We have discovered a set of small molecules able to reverse this protein clumping in the test tube. In the proposed work we aim to find related small molecules that are more active and to understand how they work. We also aim to discover whether these small molecules gain access to the brain of a mouse model, something that any AD therapeutic must be able to do. These studies will help make a major step towards understanding and developing these small molecules as 'clump busters' and potential AD therapeutics.