Soluble amyloid-β (Aβ) oligomers are key to Alzheimer’s disease (AD) pathology. Aβ oligomers constitute a significant component of senile plaques, and the presence of plaques is used to define AD.  Soluble Aβ is the most neurotoxic species; its presence correlates with AD onset and early progression. There is no current treatment to prevent the formation of neurotoxic Aβ oligomers. A proposed strategy to treat AD is the inhibition of Aβ oligomer interacting with the NMDA receptor. Disruption of NMDA receptor function and signalling molecules affect neuronal plasticity and development.

Pep63 was identified via peptide array to block the interaction between Aβ oligomers and EphB2. Mouse AD model stereotactic administration of Pep63 into the dorsal hippocampus blocked the interaction between Aβ and EphB2, as shown by co-immunoprecipitation and Western blotting. Reduced Aβ presence was detected following Pep63 treatment seen by ELIZA. Pep63 effectively reverses impaired memory deficits determined by the Morris water maze (MWM) on the AD mouse model.