Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's Disease

Abstract

Reduction of amyloid beta (Abeta) has been shown to be effective in treating Alzheimer's Disease (AD), but the underlying assumption that neurons are the main source of pathogenic Abeta; is untested. Here we challenge this prevailing belief by demonstrating that oligodendrocytes are an important source of Abeta, and play a key role in promoting abnormal neuronal hyperactivity in AD. We show that selectively suppressing oligodendrocyte Abeta production improves AD brain pathology and restores neuronal function in vivo. Our findings suggest that targeting oligodendrocyte Abeta production could be a promising therapeutic strategy for treating AD.