Kwon Hyuk Sung, Yu Hyun-Jung, Koh Seong-Ho
Department of Neurology, Hanyang University College of Medicine, Seoul, Korea.
Department of Neurology, Bundang Jesaeng General Hospital, Seongnam, Korea.
Dement Neurocogn Disord. 2024 Oct;23(4):188-201. doi: 10.12779/dnd.2024.23.4.188. Epub 2024 Oct 28.
Alzheimer's disease (AD), a leading cause of dementia, presents a formidable global health challenge intensified by the aging population. This review encapsulates the evolving landscape of AD diagnosis and treatment with a special focus on the innovative role of fluid biomarkers. Pathologically, AD is marked by amyloid beta (Aβ) plaques and neurofibrillary tangles of hyperphosphorylated tau, which lead to synaptic dysfunction, neuronal loss, and cognitive decline. These pathological changes, commencing decades before symptom onset, underscore the need for early detection and intervention. Diagnosis traditionally relies on clinical assessment, neuropsychological testing, and neuroimaging techniques. However, fluid biomarkers in cerebrospinal fluid and blood, such as various forms of Aβ, total tau, phosphorylated tau, and neurofilament light chain, are emerging as less invasive, cost-effective diagnostic tools. These biomarkers are pivotal for early diagnosis, differential diagnosis, disease progression monitoring, and treatment response evaluation. The treatment landscape is shifting toward personalized medicine, highlighted by advancements in Aβ immunotherapies, such as lecanemab and donanemab. Demonstrating efficacy in phase III clinical trials, these therapies hold promise as tailored treatment strategies based on individual biomarker profiles. The integration of fluid biomarkers into clinical practice represents a significant advance in AD management, providing the potential for early and precise diagnosis, coupled with personalized therapeutic approaches. This heralds a new era in combating this debilitating disease.
阿尔茨海默病(AD)是痴呆症的主要病因,随着人口老龄化,它给全球健康带来了严峻挑战。这篇综述概括了AD诊断和治疗的发展态势,特别关注了液体生物标志物的创新作用。在病理上,AD的特征是淀粉样β蛋白(Aβ)斑块和过度磷酸化tau蛋白的神经原纤维缠结,这些会导致突触功能障碍、神经元丧失和认知能力下降。这些病理变化在症状出现前几十年就已开始,凸显了早期检测和干预的必要性。传统的诊断依赖于临床评估、神经心理学测试和神经影像学技术。然而,脑脊液和血液中的液体生物标志物,如各种形式的Aβ、总tau蛋白、磷酸化tau蛋白和神经丝轻链,正逐渐成为侵入性较小、性价比高的诊断工具。这些生物标志物对于早期诊断、鉴别诊断、疾病进展监测和治疗反应评估至关重要。治疗格局正朝着个性化医疗转变,Aβ免疫疗法(如乐卡奈单抗和多奈单抗)的进展突显了这一点。这些疗法在III期临床试验中显示出疗效,有望成为基于个体生物标志物谱的定制治疗策略。将液体生物标志物整合到临床实践中代表了AD管理的重大进展,为早期精确诊断以及个性化治疗方法提供了可能。这预示着抗击这种使人衰弱疾病的新时代的到来。