Hossain Nabiha, Jeong Yong
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Program of Cognitive Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Dement Neurocogn Disord. 2025 Apr;24(2):75-90. doi: 10.12779/dnd.2025.24.2.75. Epub 2025 Apr 8.
Alzheimer's disease (AD), a neurodegenerative disorder characterized by the accumulation of amyloid-beta plaques and tau tangles, shows cognitive decline. Recent genetic studies have identified over 30 variants that are resilient to AD pathology, offering new therapeutic opportunities. This review explores key protective mutations of , , , , , , , , , and genes. These affect critical pathways, including lipid metabolism, synaptic function, tau regulation, and immune response. Potential treatments are discussed, including gene therapy and neuroprotective strategies, emphasizing a shift toward precision medicine focused on genetic resilience. By reviewing case studies and relevant literatures, the work explores the mechanisms by which these variants mitigate amyloid accumulation, tau pathology, neurodegeneration, and neuroinflammation, the key contributors to AD progression. Understanding these protective pathways offers critical insights into potential therapeutic applications, such as gene therapy, immune-modulating treatments, and personalized medicine approaches tailored to the individual's genetic profile. The findings highlight the potential to leverage genetic protection mechanisms to develop precision interventions for AD, offering new hope to prevent or delay disease onset and progression. These discoveries could transform future treatment strategies, shifting the focus from risk management to exploiting genetic resilience to combat AD.
阿尔茨海默病(AD)是一种神经退行性疾病,其特征为β-淀粉样蛋白斑块和tau缠结的积累,并伴有认知能力下降。最近的基因研究已经确定了30多种对AD病理具有抗性的变体,为治疗提供了新的机会。本综述探讨了 、 、 、 、 、 、 、 、 和 基因的关键保护性突变。这些突变影响关键途径,包括脂质代谢、突触功能、tau蛋白调节和免疫反应。文中讨论了潜在的治疗方法,包括基因治疗和神经保护策略,强调了向以基因抗性为重点的精准医学的转变。通过回顾案例研究和相关文献,该研究探讨了这些变体减轻淀粉样蛋白积累、tau蛋白病理、神经退行性变和神经炎症(这些是AD进展的关键因素)的机制。了解这些保护途径为潜在的治疗应用提供了关键见解,如基因治疗、免疫调节治疗以及根据个体基因特征定制的个性化医学方法。研究结果突出了利用基因保护机制开发针对AD的精准干预措施的潜力,为预防或延缓疾病发作和进展带来了新希望。这些发现可能会改变未来的治疗策略,将重点从风险管理转向利用基因抗性来对抗AD。