Despite decades of research and effort, there is still no effective disease-modifying treatment for Alzheimer’s Disease (AD). Most of the recent AD clinical trials were targeting amyloid pathway, but all these trials failed. Although amyloid pathology is a hallmark and defining feature of AD, targeting the amyloid pathway has been very challenging due to low efficacy and serious side effects. Alternative approaches or mechanisms for our understanding of the major cause of memory loss in AD need to be considered as potential therapeutic targets. Increasing studies suggest that Ca2+ dysregulation in AD plays an important role in AD pathology and is associated with other AD abnormalities, such as excessive inflammation, increased ROS, impaired autophagy, neurodegeneration, synapse, and cognitive dysfunction. Ca2+ dysregulation in cytosolic space, Endoplasmic Reticulum (ER) and mitochondria have been reported in the context of various AD models. Drugs or strategies, to correct the Ca2+ dysregulation in AD, have been demonstrated to be promising as an approach for the treatment of AD in preclinical models. This review will discuss the mechanisms of Ca2+ dysregulation in AD and associated pathology and discuss potential approaches or strategies to develop novel drugs for the treatment of AD by targeting Ca2+ dysregulation.

尽管经过数十年的研究和努力，阿尔茨海默病（AD）仍然没有有效的疾病缓解疗法。最近大多数AD临床试验都是针对淀粉样蛋白途径，但所有这些试验都失败了。尽管淀粉样蛋白病理学是 AD 的标志和定义特征，但由于疗效低且副作用严重，针对淀粉样蛋白途径一直非常具有挑战性。我们需要将了解 AD 记忆丧失主要原因的替代方法或机制视为潜在的治疗目标。越来越多的研究表明，AD 中的 Ca2+ 失调在 AD 病理学中起着重要作用，并与其他 AD 异常相关，例如过度炎症、ROS 增加、自噬受损、神经退行性变、突触和认知功能障碍。在各种 AD 模型中，已报道细胞质空间、内质网 (ER) 和线粒体中的 Ca2+ 失调。纠正 AD 中 Ca2+ 失调的药物或策略已被证明是临床前模型中治疗 AD 的一种有希望的方法。本综述将讨论 AD 中 Ca2+ 失调的机制及相关病理学，并讨论通过针对 Ca2+ 失调开发治疗 AD 的新药物的潜在方法或策略。