Research progress on mitochondrial dysfunction in Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Decades of research have confirmed that its pathological processes involve multiple organellar and molecular abnormalities, including amyloid-β (Aβ) deposition, hyperphosphorylation of Tau protein, neuroinflammation, and mitochondrial damage. Among these, mitochondrial dysfunction is widely recognized as a key early driver of AD. In the early stages of AD, significant mitochondrial oxidative damage and impaired autophagic clearance can be observed in neurons. Mitochondrial dysfunction triggers exacerbated oxidative stress, accumulation of mitochondrial DNA (mtDNA) mutations, and dysregulated fusion/fission dynamics, ultimately amplifying Aβ toxicity and promoting Tau pathology to form a vicious cycle that accelerates neuronal death. This review aims to focus on mitochondrial metabolic abnormalities, dysregulated dynamics, and the consequent microglial dysfunction. In-depth understanding of this complex network will provide crucial theoretical basis and research directions for the development of novel mitochondria-targeted therapeutic strategies for AD.