阿尔茨海默病(Alzheimer's disease, AD)是一种进行性发展的神经退行性疾病, 其发病率随人口老龄化而不断上升。AD的主要病理特征包括β-淀粉样蛋白沉积以及tau蛋白过度磷酸化导致的神经纤维缠结。线粒体分裂与融合的动态平衡是维持神经元能量代谢和细胞稳态的核心, 该平衡的破坏是AD早期的关键病理事件。线粒体动力学异常在AD 发病中至关重要, 主要表现为线粒体分裂增加和融合受损,进而引发细胞死亡和神经元损伤。本文重点讨论了β-淀粉样蛋白、 tau蛋白、APOE4和铁死亡等调控线粒体分裂与融合的病理机制, 以期为AD 的预防和治疗提供新的干预靶点。

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and its prevalence is rising in tandem with the aging of the population. The primary pathological characteristics of AD encompass the aggregation of amyloid β-protein and the formation of neurofibrillary tangles resulting from the hyperphosphorylation of tau protein. The dynamic equilibrium between mitochondrial fission and fusion is fundamental for maintaining neuronal energy metabolism and cellular homeostasis, and the disruption of this equilibrium represents a key pathological event in the early stages of AD. Aberrant mitochondrial dynamics play a critical role in the pathogenesis of AD, predominantly characterized by enhanced mitochondrial fission and impaired fusion, which subsequently induce cell death and neuronal injury. This review delves into the pathological mechanisms of mitochondrial fission and fusion regulated by amyloid β-protein, tau protein, APOE4, and ferroptosis, with the aim of providing novel intervention targets for the prevention and treatment of AD.