The pleiotropic roles of autophagy in Alzheimer's disease: From pathophysiology to therapy

Abstract

Autophagy is a lysosomal degradation pathway and the main clearance route of many toxic protein aggregates. The molecular pathology of Alzheimer's disease (AD) manifests in the form of protein aggregates-extracellular amyloid-β depositions and intracellular tau neurofibrillary tangles. Perturbations at different steps of the autophagy pathway observed in cellular and animal models of AD might contribute to amyloid-β and tau accumulation. Increased levels of autophagosomes detected in patients' brains suggest an alteration of autophagy in human disease. Autophagy is also involved in the fine-tuning of inflammation, which increases in the early stages of AD and possibly drives its pathogenesis. Mounting evidence of a causal link between impaired autophagy and AD pathology uncovers an exciting opportunity for the development of autophagy-based therapeutics.