A central role for autophagy in Alzheimer-type neurodegeneration

Abstract

The macroautophagy (autophagy) pathway is thought to be involved in a variety of neurodegenerative diseases, including Alzheimer disease (AD). It is not clear however, if autophagy plays a causative role, a protective role or is a consequence of the disease process itself. Using a Drosophila model of neuron-limited expression of AD-associated amyloid beta (Abeta) peptides, we have demonstrated an autophagy-mediated neurodegenerative cascade that is initiated by Abeta(1-42) and enhanced by aging. Our results suggest a central role for the autophagy pathway in AD type neurodegeneration and a new framework to understand seemingly unrelated AD phenotypes.