A JOURNAL OF NEUROLOGY Protection of primary neurons and mouse brain

Alzheimer’s disease is a devastating cureless neurodegenerative disorder affecting 435 million people worldwide. The disease is caused by toxic oligomers and aggregates of amyloid b protein and the microtubule-associated protein tau. Recently, the Lys-specific molecular tweezer CLR01 has been shown to inhibit aggregation and toxicity of multiple amyloidogenic proteins, including amyloid b protein and tau, by disrupting key interactions involved in the assembly process. Following up on these encouraging findings, here, we asked whether CLR01 could protect primary neurons from Alzheimer’s disease-associated synaptotoxicity and reduce Alzheimer’s disease–like pathology in vivo. Using cell culture and brain slices, we found tha