A high-throughput assay to measure amyloid-β oligomer formation

Project Summary Toxic oligomers formed by amyloid-beta (Aβ) self-association are of high interest for research into the causes and treatment of Alzheimer's Disease. Studies Aβ oligomer formation on a molecular level using biophysical and analytical techniques have provided many valuable insights, but there remain many open questions regarding oligomer structure and the factors

that influence their formation. In the present proposal, we will develop a new method for studying Aβ oligomerization that greatly diverges from the biochemical and biophysical approaches historically utilized by the field. Here, we will use a genetically encoded sensor that detects Aβ oligomer formation and converts the oligomer formation event to the expression of a

reporter gene, enabling high-throughput and direct measurements of Aβ oligomerization. This format enables us to measure the effects of millions of different factors on Aβ oligomerization and to quickly identify agents that can selectively bind oligomers over other Aβ species. 1