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MJF-14邻近连接分析可检测早期非包涵体α-突触核蛋白病变，具有更高的特异性和敏感性。

MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity.

作者信息

Jensen Nanna Møller, Fu YuHong, Betzer Cristine, Li Hongyun, Elfarrash Sara, Shaib Ali H, Krah Donatus, Vitic Zagorka, Reimer Lasse, Gram Hjalte, Buchman Vladimir, Denham Mark, Rizzoli Silvio O, Halliday Glenda M, Jensen Poul Henning

机构信息

DANDRITE - Danish Research Institute of Translational Neuroscience, Aarhus C, Denmark.

Department of Biomedicine, Aarhus University, Aarhus C, Denmark.

出版信息

NPJ Parkinsons Dis. 2024 Nov 29;10(1):227. doi: 10.1038/s41531-024-00841-9.

DOI:10.1038/s41531-024-00841-9
PMID:39613827
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11607433/
Abstract

α-Synuclein proximity ligation assay (PLA) has proved a sensitive technique for detection of non-Lewy body α-synuclein aggregate pathology. Here, we describe the MJF-14 PLA, a new PLA towards aggregated α-synuclein with unprecedented specificity, using the aggregate-selective α-synuclein antibody MJFR-14-6-4-2 (hereafter MJF-14). Signal in the assay correlates with α-synuclein aggregation in cell culture and human neurons, induced by α-synuclein overexpression or pre-formed fibrils. Co-labelling of MJF-14 PLA and pS129-α-synuclein immunofluorescence in post-mortem cases of dementia with Lewy bodies shows that while the MJF-14 PLA reveals extensive non-inclusion pathology, it is not sensitive towards pS129-α-synuclein-positive Lewy bodies. In Parkinson's disease brain, direct comparison of PLA and immunohistochemistry with the MJF-14 antibody shows widespread α-synuclein pathology preceding the formation of conventional Lewy pathology. In conclusion, we introduce an improved α-synuclein aggregate PLA to uncover abundant non-inclusion pathology, which deserves future validation with brain bank resources and in different synucleinopathies.

摘要

α-突触核蛋白邻近连接分析（PLA）已被证明是一种检测非路易小体α-突触核蛋白聚集病理学的灵敏技术。在此，我们描述了MJF-14 PLA，这是一种针对聚集的α-突触核蛋白的新型PLA，它使用聚集选择性α-突触核蛋白抗体MJFR-14-6-4-2（以下简称MJF-14），具有前所未有的特异性。该分析中的信号与细胞培养和人类神经元中由α-突触核蛋白过表达或预形成的纤维诱导的α-突触核蛋白聚集相关。在路易体痴呆的尸检病例中，对MJF-14 PLA和pS129-α-突触核蛋白免疫荧光进行共标记显示，虽然MJF-14 PLA揭示了广泛的非包涵体病理学，但它对pS129-α-突触核蛋白阳性的路易小体不敏感。在帕金森病大脑中，将PLA与使用MJF-14抗体的免疫组织化学进行直接比较，结果显示在传统路易病理学形成之前存在广泛的α-突触核蛋白病理学。总之，我们引入了一种改进的α-突触核蛋白聚集PLA，以揭示丰富的非包涵体病理学，这值得未来利用脑库资源并在不同的突触核蛋白病中进行验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26b0/11607433/abd9cd7269af/41531_2024_841_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26b0/11607433/d2f2ecd52bbc/41531_2024_841_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26b0/11607433/2003c754ff89/41531_2024_841_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26b0/11607433/a3b5f019daf9/41531_2024_841_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26b0/11607433/1ea42894ec05/41531_2024_841_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26b0/11607433/b6a1f65fbe59/41531_2024_841_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26b0/11607433/abd9cd7269af/41531_2024_841_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26b0/11607433/d2f2ecd52bbc/41531_2024_841_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26b0/11607433/2003c754ff89/41531_2024_841_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26b0/11607433/a3b5f019daf9/41531_2024_841_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26b0/11607433/1ea42894ec05/41531_2024_841_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26b0/11607433/b6a1f65fbe59/41531_2024_841_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26b0/11607433/abd9cd7269af/41531_2024_841_Fig6_HTML.jpg

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