Center for Incubation Innovation Research and Consultancy (CIIRC), Jyothy Institute of Technology, Bengaluru, India.
INSERM U1183, Laboratoire de Biochimie-Protéomique Clinique, CHU de Montpellier, Université de Montpellier, Montpellier, France.
Crit Rev Clin Lab Sci. 2020 Mar;57(2):99-113. doi: 10.1080/10408363.2019.1678011. Epub 2019 Oct 29.
Alzheimer's disease (AD) is an incurable neurodegenerative disease characterized by progressive decline of cognitive abilities. Amyloid beta peptides (Aβ), Tau proteins and the phosphorylated form of the Tau protein, p-Tau, are the core pathological biomarkers of the disease, and their detection for the diagnosis of patients is progressively being implemented. However, to date, their quantification is mostly performed on cerebrospinal fluid (CSF), the collection of which requires an invasive lumbar puncture. Early diagnosis has been shown to be important for disease-modifying treatment, which is currently in development, to limit the progression of the disease. Nevertheless, the diagnosis is often delayed to the point where the disease has already progressed, and the tools currently available do not allow for a systematic follow-up of patients. Thus, the search for a molecular signature of AD in a body fluid such as blood or saliva that can be collected in a minimally invasive way offers hope. A number of methods have been developed for the quantification of core biomarkers, especially in easily accessible fluids such as the blood, that improve their accuracy, specificity and sensitivity. This review summarizes and compares these approaches, focusing in particular on their use for Aβ detection, the earliest biomarker to be modified in the course of AD. The review also discusses biomarker quantification in CSF, blood and saliva and their clinical applications.
阿尔茨海默病（AD）是一种无法治愈的神经退行性疾病，其特征是认知能力的进行性下降。淀粉样β肽（Aβ）、Tau 蛋白和 Tau 蛋白的磷酸化形式，即 p-Tau，是该疾病的核心病理生物标志物，其检测用于诊断患者正在逐步实施。然而，迄今为止，它们的定量分析主要在脑脊液（CSF）中进行，而 CSF 的采集需要进行有创的腰椎穿刺。早期诊断已被证明对正在开发的疾病修饰治疗很重要，这种治疗可以限制疾病的进展。然而，诊断往往会被延迟到疾病已经进展的阶段，而且目前可用的工具并不能对患者进行系统的随访。因此，在血液或唾液等体液中寻找一种可通过微创方式采集的 AD 分子标志物带来了希望。已经开发了许多用于定量核心生物标志物的方法，尤其是在血液等易于获取的体液中，这些方法提高了它们的准确性、特异性和敏感性。本综述总结并比较了这些方法，特别关注它们在 Aβ检测中的应用，Aβ 是 AD 病程中最早发生改变的生物标志物。本综述还讨论了 CSF、血液和唾液中的生物标志物定量及其临床应用。
