Dual roles for autophagy: Degradation and secretion of Alzheimer's disease Aβ peptide

Alzheimer's disease (AD) is a neurodegenerative disease exhibiting amyloid beta (A beta) peptide accumulation as a key characteristic. Autophagy, which is dysregulated in AD, participates in the metabolism of A beta. Unexpectedly, we recently found that autophagy, in addition to its degradative function, also mediates the secretion of A beta. This finding adds A beta to an increasing number of biomolecules, the secretion of which is mediated by autophagy. We also showed that inhibition of A beta secretion through genetic deletion of autophagy leads to intracellular A beta accumulation, which enhanced neurodegeneration induced by autophagy deficiency. Hence, autophagy may play a central role in two pathological hallmarks of AD: A beta amyloidosis and neurodegeneration. Herein, we summarize the role of autophagy in AD with focus on A beta metabolism in light of the recently established role of autophagy in protein secretion. We discuss potential routes for autophagy-mediated A beta secretion and suggest experimental approaches to further elucidate its mechanisms.