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

Abstract

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