Autophagy Dysfunction in Alzheimer's Disease

Autophagy is a lysosome degradation pathway that turns over cytoplasmic materials and helps the cell to maintain homeostasis. Usually, it is activated under conditions of nutrient deprivation in order to enhance cell survival. Dysfunction in autophagy has been reported to contribute to several neurodegenerative diseases. Recent studies have shown that both amyloid beta precursor protein and tau protein are associated with the autophagic pathway. Abnormal processing or modification of these proteins may cause an impairment in the autophagy-lysosome pathway, which constitutively promotes the generation of amyloid beta peptides in Alzheimer's disease (AD). In addition, the impairment in the autophagy-lysosome system disturbs the turnover of other molecules associated with AD, which may also contribute to the neuronal dysfunction in AD. In this article, we have reviewed recent reports related to this topic and analyzed the dynamic changes in the autophagic pathway in AD. The findings from the studies reviewed suggest that autophagy is altered in the early stage of the disease, and dysfunction in autophagy may play an important role in the pathological process of AD. Copyright (C) 2010 S. Karger AG, Basel