Neurodegeneration Imaging Group, University of Exeter Medical School, London W12 0BZ, UK.
Invicro, Centre for Imaging Sciences, Hammersmith Hospital, London W12 0NN, UK.
Cells. 2020 Dec 2;9(12):2581. doi: 10.3390/cells9122581.
There is a need to disentangle the etiological puzzle of age-related neurodegenerative diseases, whose clinical phenotypes arise from known, and as yet unknown, pathways that can act distinctly or in concert. Enhanced sub-phenotyping and the identification of in vivo biomarker-driven signature profiles could improve the stratification of patients into clinical trials and, potentially, help to drive the treatment landscape towards the precision medicine paradigm. The rapidly growing field of neuroimaging offers valuable tools to investigate disease pathophysiology and molecular pathways in humans, with the potential to capture the whole disease course starting from preclinical stages. Positron emission tomography (PET) combines the advantages of a versatile imaging technique with the ability to quantify, to nanomolar sensitivity, molecular targets in vivo. This review will discuss current research and available imaging biomarkers evaluating dysregulation of the main molecular pathways across age-related neurodegenerative diseases. The molecular pathways focused on in this review involve mitochondrial dysfunction and energy dysregulation; neuroinflammation; protein misfolding; aggregation and the concepts of pathobiology, synaptic dysfunction, neurotransmitter dysregulation and dysfunction of the glymphatic system. The use of PET imaging to dissect these molecular pathways and the potential to aid sub-phenotyping will be discussed, with a focus on novel PET biomarkers.
有必要理清与年龄相关的神经退行性疾病的病因之谜，其临床表型源于已知和未知的途径，这些途径可以单独或协同作用。增强亚表型和确定基于体内生物标志物的特征谱可以改善患者的分层，以便进入临床试验，并有可能有助于将治疗模式推向精准医学范式。神经影像学这一日益发展的领域为研究人类疾病的病理生理学和分子途径提供了有价值的工具，有可能从临床前阶段开始捕捉整个疾病过程。正电子发射断层扫描（PET）将多功能成像技术的优势与定量的能力相结合，可达到纳摩尔灵敏度，对体内的分子靶标进行定量。这篇综述将讨论评估与年龄相关的神经退行性疾病中主要分子途径失调的当前研究和可用的成像生物标志物。本综述重点关注的分子途径包括线粒体功能障碍和能量失调；神经炎症；蛋白质错误折叠；聚集以及病理生物学、突触功能障碍、神经递质失调和糖质系统功能障碍的概念。将讨论使用 PET 成像来剖析这些分子途径以及辅助亚表型的潜力，重点介绍新的 PET 生物标志物。
