A Mitocentric View of Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disease with an increasing morbidity, mortality, and economic cost. Plaques formed by amyloid beta peptide (Aβ) and neurofibrillary tangles formed by microtubule-associated protein tau are two main characters of AD. Though previous studies have focused on Aβ and tau and got some progressions on their toxicity mechanisms, no significantly effective treatments targeting the Aβ and tau have been found. However, it is worth noting that mounting evidences showed that mitochondrial dysfunction is an early event during the process of AD pathologic changes. What is more, these studies also showed an obvious association between mitochondrial dysfunction and Aβ/tau toxicity. Furthermore, both genetic and environmental factors may increase the oxidative stress and the mitochondria are also the sensitive target of ROS, which may form a vicious feedback between mitochondrial dysfunction and oxidative stress, eventually resulting in deficient energy, synaptic failure, and cell death. This article reviews the previous related studies from different aspects and concludes the critical roles of mitochondrial dysfunction in AD, suggesting a different route to AD therapy, which may guide the research and treatment direction.