Imaging Protein Aggregates in Parkinson's Disease Serum Using Aptamer-Assisted Single-Molecule Pull-Down.
Imaging Protein Aggregates in Parkinson's Disease Serum Using Aptamer-Assisted Single-Molecule Pull-Down.
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DOI：
10.1021/acs.analchem.3c02515
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发表时间：
2023-10-17
影响因子：
7.4
通讯作者：
Klenerman, David
中科院分区：
文献类型：
--
作者：
Zhang, Yu P.;Lobanova, Evgeniia;Emin, Derya;Lobanov, Sergey V.;Kouli, Antonina;Williams-Gray, Caroline H.;Klenerman, David
可溶性α-突触核蛋白（α-syn）和淀粉样蛋白-β（Aβ）聚集体的形成与帕金森病（PD）的发生发展有关。目前的方法主要集中在聚集体浓度的测量上，并且无法确定它们的不均匀的大小和形状，由于蛋白质聚集的增加，它们在PD的发展过程中也可能发生变化。在这项工作中，我们介绍了适体辅助单分子下拉（APSiMPull）结合超分辨率荧光成像的α-syn和Aβ聚集体在人血清中的早期PD患者和年龄匹配的对照。我们的衍射限制成像结果表明，α-syn聚集体的比例（α-syn/（α-syn+Aβ））可用于区分PD组和对照组，曲线下面积（AUC）为0.85。此外，超分辨率荧光成像显示，PD血清具有比对照更高比例的更大和更圆的α-syn聚集体。观察到Aβ聚集体几乎没有差异。结合这两个指标，我们构建了一个新的生物标志物，并实现了0.90的AUC。聚集体数目与形态学的结合为PD的早期诊断提供了新的途径。
The formation of soluble α-synuclein (α-syn) and amyloid-β (Aβ) aggregates is associated with the development of Parkinson’s disease (PD). Current methods mainly focus on the measurement of the aggregate concentration and are unable to determine their heterogeneous size and shape, which potentially also change during the development of PD due to increased protein aggregation. In this work, we introduce aptamer-assisted single-molecule pull-down (APSiMPull) combined with super-resolution fluorescence imaging of α-syn and Aβ aggregates in human serum from early PD patients and age-matched controls. Our diffraction-limited imaging results indicate that the proportion of α-syn aggregates (α-syn/(α-syn+Aβ)) can be used to distinguish PD and control groups with an area under the curve (AUC) of 0.85. Further, super resolution fluorescence imaging reveals that PD serums have a higher portion of larger and rounder α-syn aggregates than controls. Little difference was observed for Aβ aggregates. Combining these two metrics, we constructed a new biomarker and achieved an AUC of 0.90. The combination of the aggregate number and morphology provides a new approach to early PD diagnosis.
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影响因子：
16.8
作者：
Mackmull, Marie-Therese;Nagel, Luise;Picotti, Paola
通讯作者：
Picotti, Paola
影响因子：
21.8
作者：
Di Antonio M;Ponjavic A;Radzevičius A;Ranasinghe RT;Catalano M;Zhang X;Shen J;Needham LM;Lee SF;Klenerman D;Balasubramanian S
通讯作者：
Balasubramanian S
DOI：
10.3791/50549
发表时间：
2014-04-24
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Chandradoss SD;Haagsma AC;Lee YK;Hwang JH;Nam JM;Joo C
通讯作者：
Joo C
影响因子：
14.5
作者：
Lobanova, Evgeniia;Whiten, Daniel;Ruggeri, Francesco S.;Taylor, Christopher G.;Kouli, Antonina;Xia, Zengjie;Emin, Derya;Zhang, Yu P.;Lam, Jeff Y. L.;Williams-Gray, Caroline H.;Klenerman, David
通讯作者：
Klenerman, David
影响因子：
3.4
作者：
Chang, Chun-Wei;Yang, Shieh-Yueh;Wu, Yih-Ru
通讯作者：
Wu, Yih-Ru