Evidence that a synthetic amyloid-? oligomer-binding peptide (ABP) targets amyloid-? deposits in transgenic mouse brain and human Alzheimer's disease brain

摘要

The synthetic ~5kDa ABP (amyloid-? binding peptide) consists of a region of the 228kDa human pericentrioloar material-1 (PCM-1) protein that selectively and avidly binds in vitro Aβ1-42 oligomers, believed to be key co-drivers of Alzheimer's disease (AD), but not monomers (Chakravarthy et al., (2013) [3]). ABP also prevents A?1-42 from triggering the apoptotic death of cultured human SHSY5Y neuroblasts, likely by sequestering A? oligomers, suggesting that it might be a potential AD therapeutic. Here we support this possibility by showing that ABP also recognizes and binds Aβ1-42 aggregates in sections of cortices and hippocampi from brains of AD transgenic mice and human AD patients. More importantly, ABP targets Aβ1-42 aggregates when microinjected into the hippocampi of the brains of live AD transgenic mice.