Catafau Ana M, Bullich Santiago
Piramal Imaging GmbH, Tegeler Straße 6-7, 13353 Berlin, Germany.
Curr Alzheimer Res. 2017;14(2):169-177. doi: 10.2174/1567205013666160620111408.
Clinical classifications of neurodegenerative disorders are often based on neuropathology. The term "proteinopathies" includes disorders that have in common abnormal proteins as a hallmark, e.g. amyloidoses, tauopathies, synucleopathies, ubiquitinopathies. Different proteins can also co-exist in the same disease. To further complicate the pathophysiology scenario, not only different proteins, but also cells are believed to play an active role in neurodegeneration, in particular those participating in neuroinflammatory processes in the brain, such as activated microglia and astrocytes. In clinical practice, differentiating pathophysiology from clinical symptoms to allow accurate clinical classification of these disorders during life, becomes difficult in absence of biomarkers for these pathology hallmarks. PET imaging can be a useful tool in this context. Using PET tracers targeting misfolded proteins it will be possible to identify the presence or absence of the target, to depict the cerebral distribution and to quantify the protein load in different cerebral regions, as well as to monitor changes over time. Beta-amyloid is one of the proteins involved in neurodegenerative disorders, which is currently suitable to be imaged by means of PET. Research efforts are currently ongoing in order to identify new PET tracers targeting non-amyloid PET tracers for neurodegeneration. This article will focus on the investigational PET tracers targeting tau and alpha-synuclein as misfolded proteins, and activated microglia and astrocytes as cellular targets for neuroinflammation. An overview of target characteristics, development challenges, clinical relevance and current status of human PET imaging is provided.
神经退行性疾病的临床分类通常基于神经病理学。“蛋白病”一词包括以异常蛋白质为特征的疾病，例如淀粉样变性病、tau蛋白病、突触核蛋白病、泛素蛋白病。不同的蛋白质也可在同一种疾病中共存。使病理生理情况更加复杂的是，不仅不同的蛋白质，而且细胞也被认为在神经退行性变中起积极作用，特别是那些参与大脑神经炎症过程的细胞，如活化的小胶质细胞和星形胶质细胞。在临床实践中，由于缺乏这些病理特征的生物标志物，在疾病存活期从临床症状中区分病理生理情况以进行准确的临床分类变得困难。在这种情况下，正电子发射断层显像（PET）成像可能是一种有用的工具。使用针对错误折叠蛋白质的PET示踪剂，将有可能识别目标的存在与否，描绘大脑分布并量化不同脑区的蛋白质负荷，以及监测随时间的变化。β-淀粉样蛋白是参与神经退行性疾病的蛋白质之一，目前适合通过PET进行成像。目前正在进行研究以确定针对神经退行性变的非淀粉样PET示踪剂的新PET示踪剂。本文将重点关注针对tau蛋白和α-突触核蛋白作为错误折叠蛋白质，以及活化的小胶质细胞和星形胶质细胞作为神经炎症细胞靶点的研究性PET示踪剂。提供了靶点特征、开发挑战、临床相关性和人类PET成像现状的概述。
