Zinc is the second abundant trace element in the human central nervous system (CNS). Zinc homeostasis is impaired in the elderly population and Alzheimer’s disease (AD) patients. Due to the failures of β-amyloid (Aβ)- and microtubule-associated protein tau (MAP-tau, tau)-targeting drugs, many researchers consider AD as a multifactorial disease. Emerging evidence demonstrates that zinc is also widely associated with the development of AD. Zinc dyshomeostasis hypothesis of AD has been proposed. In this review, we summarize the role of zinc in Aβ production, protein quality control, redox homeostasis, tau phosphorylation, and BDNF signaling. Due to the multifunctional roles of zinc, when zinc dyshomeostasis occurs, it may influence these different biological activities. Zinc dyshomeostasis could be a therapeutic target for AD treatment. However, there is no consensus on the zinc concentration alteration and the effect of zinc overload or zinc deficiency in AD patients, mouse models and cell lines. Given these significant differences across reported studies, it still needs a long time for clinical application in the treatment of AD.

锌是人类中枢神经系统（CNS）中的第二种丰富的微量元素。锌稳态在老年人和阿尔茨海默氏病（AD）患者中受损。由于β-淀粉样蛋白（Aβ）和微管相关蛋白tau（MAP-tau，tau）靶向药物的失败，许多研究人员认为AD是一种多因素疾病。新兴证据表明锌也与AD的发展广泛相关。已经提出了AD的锌动态异常假说。在这篇综述中，我们总结了锌在Aβ生产，蛋白质质量控​​制，氧化还原稳态，tau磷酸化和BDNF信号传导中的作用。由于锌的多功能作用，当锌动态不平衡发生时，它可能会影响这些不同的生物活性。锌动态异常可能是AD治疗的治疗目标。然而，对于AD患者，小鼠模型和细胞系中的锌浓度变化以及锌超载或锌缺乏的影响尚无共识。鉴于已报道的研究之间存在这些显着差异，因此在AD的治疗中仍需要长时间的临床应用。