Alzheimer’s disease (AD) is the most common late-onset dementia characterized by the deposition of extracellular amyloid plaques and formation of intracellular neurofibrillary tangles, which eventually lead to neuronal loss and cognitive deficits. Multiple lines of evidence indicate that mitochondrial dysfunction is involved in the initiation and progression of AD. As essential machinery for mitochondrial quality control, mitophagy plays a housekeeping role in neuronal cells by eliminating dysfunctional or excessive mitochondria. At present, mounting evidence support that the activity of mitophagy markedly declines in human brains during aging. Impaired mitophagy and mitochondrial dysfunction were causally linked to bioenergetic deficiency, oxidative stress, microglial activation, and chronic inflammation, thereby aggravating the Aβ and tau pathologies and leading to neuron loss in AD. This review summarizes recent evidence for age-associated mitophagy decline during human aging and provides an overview of mitochondrial dysfunction involved in the process of AD. It also discusses the underlying mechanisms through which defective mitophagy leads to neuronal cell death in AD. Therapeutic interventions aiming to restore mitophagy functions can be used as a strategy for ameliorating AD pathogenesis.

阿尔茨海默病 (AD) 是最常见的迟发性痴呆，其特征是细胞外淀粉样斑块的沉积和细胞内神经原纤维缠结的形成，最终导致神经元丢失和认知缺陷。多项证据表明，线粒体功能障碍与 AD 的发生和进展有关。作为线粒体质量控制的重要机制，线粒体自噬通过消除功能失调或过量的线粒体在神经元细胞中发挥看家作用。目前，越来越多的证据支持人类大脑在衰老过程中线粒体自噬活动显着下降。线粒体自噬受损和线粒体功能障碍与生物能缺乏、氧化应激、小胶质细胞激活和慢性炎症有因果关系，从而加重 Aβ 和 tau 病理并导致 AD 中的神经元丢失。本综述总结了人类衰老过程中与年龄相关的线粒体自噬下降的最新证据，并概述了 AD 过程中涉及的线粒体功能障碍。它还讨论了有缺陷的线粒体自噬导致 AD 神经元细胞死亡的潜在机制。旨在恢复线粒体自噬功能的治疗干预可用作改善 AD 发病机制的策略。