Department of Pharmacology and Clinical Pharmacology, Research Center for Controlling Intercellular Communication, Inha University, Incheon, South Korea.
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
Clin Chem. 2023 Nov 2;69(11):1247-1259. doi: 10.1093/clinchem/hvad139.
Development of validated biomarkers to detect early Alzheimer disease (AD) neuropathology is needed for therapeutic AD trials. Abnormal concentrations of "core" AD biomarkers, cerebrospinal fluid (CSF) amyloid beta1-42, total tau, and phosphorylated tau correlate well with neuroimaging biomarkers and autopsy findings. Nevertheless, given the limitations of established CSF and neuroimaging biomarkers, accelerated development of blood-based AD biomarkers is underway.
Here we describe the clinical significance of CSF and plasma AD biomarkers to detect disease pathology throughout the Alzheimer continuum and correlate with imaging biomarkers. Use of the AT(N) classification by CSF and imaging biomarkers provides a more objective biologically based diagnosis of AD than clinical diagnosis alone. Significant progress in measuring CSF AD biomarkers using extensively validated highly automated assay systems has facilitated their transition from research use only to approved in vitro diagnostics tests for clinical use. We summarize development of plasma AD biomarkers as screening tools for enrollment and monitoring participants in therapeutic trials and ultimately in clinical care. Finally, we discuss the challenges for AD biomarkers use in clinical trials and precision medicine, emphasizing the possible ethnocultural differences in the levels of AD biomarkers.
CSF AD biomarker measurements using fully automated analytical platforms is possible. Building on this experience, validated blood-based biomarker tests are being implemented on highly automated immunoassay and mass spectrometry platforms. The progress made developing analytically and clinically validated plasma AD biomarkers within the AT(N) classification scheme can accelerate use of AD biomarkers in therapeutic trials and routine clinical practice.
为了进行治疗阿尔茨海默病（AD）的临床试验，需要开发经过验证的生物标志物来检测早期 AD 神经病理学。“核心”AD 生物标志物（脑脊液 [CSF] 中的β淀粉样蛋白 1-42、总 tau 和磷酸化 tau）的异常浓度与神经影像学生物标志物和尸检结果密切相关。尽管如此，鉴于已建立的 CSF 和神经影像学生物标志物的局限性，正在加速开发基于血液的 AD 生物标志物。
本文描述了 CSF 和血浆 AD 生物标志物在检测 AD 连续体中疾病病理学以及与影像学生物标志物的相关性方面的临床意义。通过 CSF 和影像学生物标志物的 AT（N）分类，可以提供比单独临床诊断更客观的基于生物学的 AD 诊断。使用经过广泛验证的高度自动化检测系统测量 CSF AD 生物标志物方面取得了重大进展，这使得它们从仅用于研究的试剂过渡到了批准的用于临床使用的体外诊断测试。我们总结了血浆 AD 生物标志物作为筛选工具，用于纳入和监测治疗试验中的参与者，最终用于临床护理。最后，我们讨论了 AD 生物标志物在临床试验和精准医学中的应用面临的挑战，强调了 AD 生物标志物水平可能存在的种族文化差异。
使用全自动分析平台进行 CSF AD 生物标志物测量是可行的。在此基础上，经过验证的基于血液的生物标志物测试正在高度自动化的免疫测定和质谱平台上实施。在 AT（N）分类方案内，在分析和临床验证的血浆 AD 生物标志物方面取得的进展可以加速 AD 生物标志物在治疗试验和常规临床实践中的应用。
