Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, People's Republic of China.
National Clinical Research Center for Geriatric Diseases, Beijing, People's Republic of China.
J Alzheimers Dis. 2021;81(1):19-32. doi: 10.3233/JAD-201068.
Alzheimer's disease (AD) research is entering a unique moment in which enormous information about the molecular basis of this disease is being translated into therapeutics. However, almost all drug candidates have failed in clinical trials over the past 30 years. These many trial failures have highlighted a need for the incorporation of biomarkers in clinical trials to help improve the trial design. Fluid biomarkers measured in cerebrospinal fluid and circulating blood, which can reflect the pathophysiological process in the brain, are becoming increasingly important in AD clinical trials. In this review, we first succinctly outline a panel of fluid biomarkers for neuropathological changes in AD. Then, we provide a comprehensive overview of current and future application of fluid biomarkers in clinical trials for AD. We also summarize the many challenges that have been encountered in efforts to integrate fluid biomarkers in clinical trials, and the barriers that have begun to be overcome. Ongoing research efforts in the field of fluid biomarkers will be critical to make significant progress in ultimately unveiling disease-modifying therapies in AD.
阿尔茨海默病（AD）的研究正进入一个独特的时期，大量关于这种疾病分子基础的信息正在转化为治疗方法。然而，在过去的 30 年中，几乎所有的候选药物都在临床试验中失败了。这些多次试验失败凸显了在临床试验中纳入生物标志物以帮助改善试验设计的必要性。在 AD 临床试验中，脑脊液和循环血液中测量的液体生物标志物，能够反映大脑中的病理生理过程，正变得越来越重要。在这篇综述中，我们首先简要概述了一组 AD 神经病理学变化的液体生物标志物。然后，我们全面概述了当前和未来 AD 临床试验中液体生物标志物的应用。我们还总结了在将液体生物标志物纳入临床试验方面所遇到的许多挑战，以及开始克服的障碍。该领域的液体生物标志物的持续研究对于在 AD 中最终揭示疾病修饰疗法的研究具有至关重要的意义。
