Defective Autophagy and Mitophagy in Alzheimer's Disease: Mechanisms and Translational Implications

The main histopathology of Alzheimer's disease (AD) is featured by the extracellular accumulation of amyloid-beta (A beta) plaques and intracellular tau neurofibrillary tangles (NFT) in the brain, which is likely to result from co-pathogenic interactions among multiple factors, e.g., aging or genes. The link between defective autophagy/mitophagy and AD pathologies is still under investigation and not fully established. In this review, we consider how AD is associated with impaired autophagy and mitophagy, and how these impact pathological hallmarks as well as the potential mechanisms. This complicated interplay between autophagy or mitophagy and histopathology in AD suggests that targeting autophagy or mitophagy probably is a promising anti-AD drug candidate. Finally, we review the implications of some new insights for induction of autophagy or mitophagy as the new therapeutic way that targets processes upstream of both NFT and A beta plaques, and hence stops the neurodegenerative course in AD.

Automated summary

The main histopathology of Alzheimer's disease is characterized by the accumulation of Aβ plaques and tau neurofibrillary tangles in the brain, likely resulting from interactions among various factors. The link between defective autophagy/mitophagy and AD pathologies is still being investigated, suggesting that targeting autophagy/mitophagy may be a promising anti-AD drug candidate. The complex interplay between autophagy or mitophagy and histopathology in AD implies that inducing autophagy/mitophagy could potentially stop the neurodegenerative course in AD by targeting processes upstream of both NFT and Aβ plaques.