阿尔茨海默病中的淀粉样蛋白生物标志物。

Amyloid biomarkers in Alzheimer's disease.

机构信息

Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; The Torsten Söderberg Professorship at the Royal Swedish Academy of Sciences.

Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden; Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.

出版信息

Trends Pharmacol Sci. 2015 May;36(5):297-309. doi: 10.1016/j.tips.2015.03.002. Epub 2015 Apr 1.

DOI:10.1016/j.tips.2015.03.002

PMID:25840462

Abstract

Aggregation of amyloid-β (Aβ) into oligomers, fibrils, and plaques is central in the molecular pathogenesis of Alzheimer's disease (AD), and is the main focus of AD drug development. Biomarkers to monitor Aβ metabolism and aggregation directly in patients are important for further detailed study of the involvement of Aβ in disease pathogenesis and to monitor the biochemical effect of drugs targeting Aβ in clinical trials. Furthermore, if anti-Aβ disease-modifying drugs prove to be effective clinically, amyloid biomarkers will be of special value in the clinic to identify patients with brain amyloid deposition at risk for progression to AD dementia, to enable initiation of treatment before neurodegeneration is too severe, and to monitor drug effects on Aβ metabolism or pathology to guide dosage. Two types of amyloid biomarker have been developed: Aβ-binding ligands for use in positron emission tomography (PET) and assays to measure Aβ42 in cerebrospinal fluid (CSF). In this review, we present the rationales behind these biomarkers and compare their ability to measure Aβ plaque load in the brain. We also review possible shortcomings and the need of standardization of both biomarkers, as well as their implementation in the clinic.

摘要

淀粉样蛋白-β（Aβ）聚集成寡聚物、原纤维和斑块是阿尔茨海默病（AD）发病机制的核心，也是 AD 药物开发的主要关注点。生物标志物可直接在患者体内监测 Aβ的代谢和聚集，对于进一步深入研究 Aβ在疾病发病机制中的作用以及监测针对 Aβ的药物的生化作用非常重要。此外，如果抗 Aβ的疾病修饰药物在临床上被证明有效，那么淀粉样蛋白生物标志物在临床上具有特殊的价值，可以识别有进展为 AD 痴呆风险的大脑淀粉样蛋白沉积患者，以便在神经退行性变过于严重之前开始治疗，并监测药物对 Aβ代谢或病理学的影响，以指导剂量。已经开发了两种类型的淀粉样蛋白生物标志物：用于正电子发射断层扫描（PET）的 Aβ结合配体和测量脑脊液（CSF）中 Aβ42 的测定法。在这篇综述中，我们介绍了这些生物标志物背后的原理，并比较了它们测量大脑中 Aβ斑块负荷的能力。我们还回顾了这两种生物标志物可能存在的缺陷以及标准化的必要性，以及它们在临床上的应用。