Department of Neurology, Seoul National University College of Medicine and Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
Department of Neurology, Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Republic of Korea.
J Alzheimers Dis. 2020;75(3):685-696. doi: 10.3233/JAD-200104.
Amyloid-β (Aβ) is a key protein in Alzheimer's disease (AD) in that its accumulation induces complex pathological changes. Although there has been extensive research on the metabolism of Aβ in AD, new compelling results have recently emerged. Historically, the production and clearance of Aβ have been thought to originate in the central nervous system (CNS). However, recent evidence suggests that the production and clearance of Aβ can also occur in the peripheral system, and that the peripherally driven Aβ migrates to the CNS and induces amyloidopathy with subsequent AD pathologic changes in the brain. This concept implies that AD is not restricted to the CNS but is a systemic disease instead. As such, the development of blood-based biomarkers targeting Aβ is of great interest. Central and peripheral Aβ are both active contributors to the pathology of AD and interact bidirectionally. Measuring peripheral Aβ is not just observing the reflection of the residual Aβ removed from the CNS but also tracking the ongoing process of AD pathology. Additionally, blood-based biomarkers could be a more accessible tool in clinical and research settings. Through arduous research, several blood-based biomarker assays have demonstrated notable results. In this review, we describe the metabolism of Aβ and the amyloid-targeting blood-based biomarkers of AD.
淀粉样蛋白-β（Aβ）是阿尔茨海默病（AD）的关键蛋白，其积累诱导了复杂的病理变化。尽管对 AD 中 Aβ的代谢进行了广泛的研究，但最近出现了新的令人信服的结果。从历史上看，Aβ的产生和清除被认为起源于中枢神经系统（CNS）。然而，最近的证据表明，Aβ的产生和清除也可以发生在外周系统中，并且外周驱动的 Aβ迁移到中枢神经系统，并在大脑中诱导淀粉样变病理变化，随后发生 AD 病理变化。这一概念意味着 AD 不仅限于中枢神经系统，而是一种全身性疾病。因此，针对 Aβ的基于血液的生物标志物的开发具有重要意义。中枢和外周 Aβ都是 AD 病理学的积极贡献者，并相互双向作用。测量外周 Aβ不仅是观察从中枢神经系统清除的残留 Aβ的反映，也是跟踪 AD 病理学的进行过程。此外，基于血液的生物标志物可能是临床和研究环境中更易于使用的工具。通过艰苦的研究，几种基于血液的生物标志物检测方法已经取得了显著的结果。在这篇综述中，我们描述了 Aβ的代谢以及 AD 的靶向淀粉样蛋白的基于血液的生物标志物。
