(750a) Modulating Amyloid-Beta Aggregation and Neurotoxicity by a New Family of Small Molecules

Alzheimer's disease (AD) is a degenerative illness that impairs memory, thinking and behavior. The accumulation of insoluble amyloid aggregates, composed primarily of the neurotoxic amyloid-beta peptide, is a hallmark of AD. Although amyloid-beta monomer is soluble and non-toxic, soluble amyloid-beta oligomers are known to be primary toxic species in AD. Therefore, modulation of amyloid-beta oligomerization is considered a promising therapeutic strategy to prevent or treat AD. Beyond therapeutic impact, recently discovered aggregation modulators have also enhanced our understanding of AD pathogenic mechanism. Despite these advances, an effective therapeutic to AD is still unavailable. Therefore, there remains a need to discover new chemical classes of safe and effective modulators. In order to search for safe small molecule inhibitors, we screened a family of compounds that are typically used for other purposes. Our results show that several compounds tested were effective in modulating amyloid-beta aggregation and neurotoxicity in vitro. The small molecules identified will serve as drug leads to cure AD.