Retromer enhancement rescues endosomal recycling defects induced by SORL1 deficiency

Our work shows that treatment with a small molecule that increases retromer expression in vitro and enhances retromer-related trafficking can reduce important cellular and neuropathologic phenotypes in human AD neuronal models. Using TPT-260, we broadly show that enhancement of retromer-related trafficking can fully or partially rescue deficits induced by loss of SORL1. This study builds on previous work that has used these and other retromer-targeting small molecules in animals and human cells, suggesting that studies such as this could represent an important preclinical step in identifying new therapeutic molecules for AD.