McGill Centre for Studies in Aging (MCSA), McGill University, Montreal, QC, Canada.
Mol Diagn Ther. 2011 Dec 1;15(6):313-25. doi: 10.1007/BF03256467.
Research progress during the last decades has resulted in an unprecedented accumulation of knowledge regarding the molecular pathogenesis of Alzheimer disease (AD). These important achievements toward clarifying the mechanistic processes underlying AD are being translated into ongoing development of biomarkers and their use in clinical trials. AD biomarkers are biochemical and anatomical variables (e.g. cerebrospinal fluid, positron emission tomography, and structural MRI) that measure AD-related pathologic features (i.e. amyloid deposition and neurodegeneration) in vivo. Biomarkers are utilized as 'diagnostic biomarkers' and/or 'endpoint biomarkers' in symptomatic or disease-modifying clinical trials. Diagnostic biomarkers play an important role in population enrichment by refining selection criteria, stratifying populations, and increasing the statistical power of trials. Endpoint biomarkers may be used as outcome measures to monitor the rate of disease progression and detect treatment effects. AD biomarkers do not reach abnormal levels or peak simultaneously, but do so in a time-dependent order. The choice of biomarkers for a clinical trial must take into consideration the type of therapeutic intervention, the clinical stage of AD, and the time dependence of biomarker changes during disease progression. The combination of amyloid and neurodegeneration biomarkers is highly desirable since they capture different aspects of the disease. Clinical trials for every clinical stage of AD would benefit from quantification and standardization of biomarkers. However, this is still a work in progress.
在过去几十年的研究中，阿尔茨海默病（AD）的分子发病机制方面的知识得到了前所未有的积累。这些对于阐明 AD 潜在机制过程的重要成果正在转化为生物标志物的持续开发及其在临床试验中的应用。AD 生物标志物是衡量 AD 相关病理特征（即淀粉样蛋白沉积和神经退行性变）的生化和解剖变量（例如脑脊液、正电子发射断层扫描和结构 MRI）。生物标志物可用作有症状或疾病修饰临床试验中的“诊断生物标志物”和/或“终点生物标志物”。诊断生物标志物通过细化选择标准、分层人群和提高试验的统计效力，在人群富集中发挥着重要作用。终点生物标志物可用作监测疾病进展速度和检测治疗效果的指标。AD 生物标志物不会同时达到异常水平或达到峰值，而是按照时间依赖性顺序出现。选择临床试验中的生物标志物时，必须考虑治疗干预的类型、AD 的临床阶段以及疾病进展过程中生物标志物变化的时间依赖性。淀粉样蛋白和神经退行性变生物标志物的结合是非常可取的，因为它们捕捉到了疾病的不同方面。每个 AD 临床阶段的临床试验都将受益于生物标志物的量化和标准化。然而，这仍然是一个正在进行的工作。
