IRCCS Fondazione Don Carlo Gnocchi, Via Capecelatro 66, Milan, Italy.
IRCCS Fondazione Don Carlo Gnocchi, Via Capecelatro 66, Milan, Italy.
J Pharm Biomed Anal. 2021 Jan 5;192:113649. doi: 10.1016/j.jpba.2020.113649. Epub 2020 Sep 23.
One of the main hurdles in the study of Alzheimer's Disease (AD) is the lack of easily accessible and sensitive biomarkers for the diagnosis, the prediction of the disease progression rate and the evaluation of rehabilitative and pharmacological treatments. Extracellular Vesicles (EVs) are nanoscale particles released by body cells, studied as promising biomarkers of AD as they are involved in the onset and progression of the disease. In the strive for a reliable and sensitive method to analyze EVs, we applied our recently developed biosensor based on Surface Plasmon Resonance imaging (SPRi) technology for the identification and profiling of neural EVs populations circulating in the plasma of 10 AD patients and 10 healthy subjects. The SPRi-array was designed to separate simultaneously EVs released by neurons, astrocytes, microglia and oligodendrocytes, and to evaluate the presence and the relative amount of specific surface molecules related to pathological processes including translocator protein (TSPO), β-Amyloid and ganglioside M1. As results, significant variations in the relative amount and cargoes of specific brain-derived populations of EVs were observed comparing EVs coming from AD patients and healthy subjects, finding the main differences in the activation phenotype of microglia EVs, in the lipid moieties on generic EVs and in the β-Amyloid expression on surfaces of neuronal EVs. Besides, the demonstrated correlation of SPRi data with Magnetic Resonance Imaging analysis, provided support for using the SPRi-based biosensor for the evaluation of neurodegeneration detecting and characterizing circulating EVs as peripheral biomarkers for the diagnosis and monitoring of progression and rehabilitation treatments in AD patients.
阿尔茨海默病（AD）研究的主要障碍之一是缺乏易于获取和敏感的生物标志物，用于诊断、预测疾病进展速度以及评估康复和药物治疗效果。细胞外囊泡（EVs）是细胞释放的纳米级颗粒，作为 AD 的有前途的生物标志物进行研究，因为它们参与了疾病的发生和进展。为了寻求一种可靠和敏感的 EVs 分析方法，我们应用了我们最近开发的基于表面等离子体共振成像（SPRi）技术的生物传感器，用于鉴定和分析在 10 名 AD 患者和 10 名健康受试者血浆中循环的神经 EVs 群体。SPRi 阵列被设计用于同时分离神经元、星形胶质细胞、小胶质细胞和少突胶质细胞释放的 EVs，并评估与病理过程相关的特定表面分子的存在和相对数量，包括转位蛋白（TSPO）、β-淀粉样蛋白和神经节苷脂 M1。结果表明，与健康受试者相比，来自 AD 患者的 EVs 中存在相对数量和特定脑源性 EVs 货物的显著差异，在小胶质细胞 EVs 的激活表型、通用 EVs 的脂质部分以及神经元 EVs 表面的β-淀粉样蛋白表达方面发现了主要差异。此外，SPRi 数据与磁共振成像分析的相关性表明，使用基于 SPRi 的生物传感器评估神经退行性变、检测和表征循环 EVs 作为 AD 患者诊断和监测进展和康复治疗的外周生物标志物具有一定的可行性。
