Li Danni, Mielke Michelle M
Department of Lab Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
Neurol Ther. 2019 Dec;8(Suppl 2):73-82. doi: 10.1007/s40120-019-00164-5. Epub 2019 Dec 12.
The development of blood-based biomarkers of Alzheimer's disease (AD) pathology as tools for screening the general population, and as the first step in a multistep process to determine which non-demented individuals are at greatest risk of developing AD dementia, is essential. Proteins that are reflective of AD pathology, such as amyloid beta 42 (Aβ), tau proteins [total tau (T-tau) and phosphorylated tau (P-tau)], and neurofilament light chain (NfL), are detectable in the blood. However, a major challenge in measuring these blood-based proteins is that their concentrations are much lower in plasma or serum than in the cerebrospinal fluid. Single molecule array (SiMoA) is an ultrasensitive technology that can detect proteins in blood at sub-femtomolar concentrations (i.e., 10 M). In this review, we focus on the utility of SiMoA assays for the measurement of plasma or serum Aβ, P-tau, T-tau, and NfL levels and discuss future directions.
开发基于血液的阿尔茨海默病(AD)病理学生物标志物,作为筛查普通人群的工具,并作为多步骤过程的第一步,以确定哪些非痴呆个体患AD痴呆的风险最大,这至关重要。反映AD病理学的蛋白质,如β淀粉样蛋白42(Aβ)、tau蛋白[总tau(T-tau)和磷酸化tau(P-tau)]以及神经丝轻链(NfL),在血液中是可检测的。然而,测量这些基于血液的蛋白质的一个主要挑战是,它们在血浆或血清中的浓度比在脑脊液中低得多。单分子阵列(SiMoA)是一种超灵敏技术,能够检测血液中亚飞摩尔浓度(即10⁻¹⁵M)的蛋白质。在本综述中,我们重点关注SiMoA检测在测量血浆或血清Aβ、P-tau、T-tau和NfL水平方面的应用,并讨论未来的方向。