Abstract:

Alzheimer's disease （AD） is the most common neurodegenerative disease. MicroRNAs （miRNAs）， as important molecules regulating gene expression， play a key role in neurodegenerative diseases. This review summarized the research progress on the pathological association mechanisms between miRNAs and AD， as well as their relevance to early diagnosis. It focused on exploring the critical regulatory roles of miRNAs in the core pathological processes of AD， such as regulating the production of β-amyloid （Aβ） by targeting genes like β-site amyloid precursor protein cleaving enzyme 1 （BACE1）， affecting the phosphorylation process of Tau protein by regulating kinases like microtubule affinity regulating kinase 1 （MARK1） and cyclin-dependent kinase 5 （CDK5）， and extensively participating in the regulation of neuroinflammation （e.g.， miR-155， miR-146a） and oxidative stress （e.g.， miR-34a）. Meanwhile， this review summarized the great potential of miRNAs as AD biomarkers and discussed the current challenges and future directions， aiming to provide references for the research and clinical treatment of Alzheimer's disease.

Key words: microRNA, Alzheimer's disease, pathological association mechanism, early diagnosis, biomarker

摘要：

阿尔茨海默病（Alzheimer's disease, AD）是最常见的神经退行性疾病，微小核糖核酸（microRNA, miRNA）作为调控基因表达的重要分子，在神经退行性疾病中发挥着关键作用。综述了miRNA与AD病理的关联机制及早期诊断相关的研究进展，重点探讨了miRNA在AD核心病理环节中的关键调控作用，如通过靶向β-淀粉样前体蛋白裂解酶1（β-site amyloid precursor protein cleaving enzyme 1，BACE1）等基因调控β-淀粉样蛋白（Aβ）的生成、调控微管亲和调节激酶1（microtubule affinity regulating kinase 1，MARK1）、细胞周期蛋白依赖性激酶4（cyclin-dependent kinase 5，CDK5）等激酶影响Tau蛋白的磷酸化进程，以及广泛参与神经炎症（如miR-155、miR-146a）与氧化应激（如miR-34a）的调节等。同时，总结了miRNA作为AD生物标志物的巨大潜力，并讨论了当前研究面临的挑战与未来方向，以期为阿尔茨海默病的研究与临床治疗提供参考。

关键词: microRNA, 阿尔茨海默病, 病理关联机制, 早期诊断, 生物标志物