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

Abstract

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