Ex vivo target engagement of the Abeta oligomer disassembling compound RD2 in patient derived brain homogenates

Soluble Aβ oligomers are highly toxic and may be responsible for development and progression of Alzheimer’s disease (AD). Elimination of Aβ oligomers is therefore a promising therapeutic strategy. The compound RD2 was developed to stabilize Aβ monomers in their native conformation, which is very close to an intrinsically disordered protein (IDP). RD2 has demonstrated already to directly eliminate soluble Aβ oligomers in vitro and in vivo and to improve cognition or decelerate neurodegeneration in four different animal models in four different laboratories 1,2. Here, we wanted to test if RD2 is able to disassemble Aβ oligomers obtained from AD patient derived brain tissue.