MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity
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 an...
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Nature Portfolio
2024-11-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-024-00841-9 |
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| author | Nanna Møller Jensen YuHong Fu Cristine Betzer Hongyun Li Sara Elfarrash Ali H. Shaib Donatus Krah Zagorka Vitic Lasse Reimer Hjalte Gram Vladimir Buchman Mark Denham Silvio O. Rizzoli Glenda M. Halliday Poul Henning Jensen |
| author_facet | Nanna Møller Jensen YuHong Fu Cristine Betzer Hongyun Li Sara Elfarrash Ali H. Shaib Donatus Krah Zagorka Vitic Lasse Reimer Hjalte Gram Vladimir Buchman Mark Denham Silvio O. Rizzoli Glenda M. Halliday Poul Henning Jensen |
| author_sort | Nanna Møller Jensen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c55cdec6dd264aa8b793c43fcfeb0013 |
| institution | Kabale University |
| issn | 2373-8057 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-c55cdec6dd264aa8b793c43fcfeb00132024-12-01T12:15:05ZengNature Portfolionpj Parkinson's Disease2373-80572024-11-0110112110.1038/s41531-024-00841-9MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivityNanna Møller Jensen0YuHong Fu1Cristine Betzer2Hongyun Li3Sara Elfarrash4Ali H. Shaib5Donatus Krah6Zagorka Vitic7Lasse Reimer8Hjalte Gram9Vladimir Buchman10Mark Denham11Silvio O. Rizzoli12Glenda M. Halliday13Poul Henning Jensen14DANDRITE - Danish Research Institute of Translational NeuroscienceBrain and Mind Centre & Faculty of Medicine and Health, School of Medical Sciences, University of SydneyDANDRITE - Danish Research Institute of Translational NeuroscienceBrain and Mind Centre & Faculty of Medicine and Health, School of Medical Sciences, University of SydneyDANDRITE - Danish Research Institute of Translational NeuroscienceDepartment of Neuro- and Sensory Physiology, University Medical Center GöttingenDepartment of Neuro- and Sensory Physiology, University Medical Center GöttingenDANDRITE - Danish Research Institute of Translational NeuroscienceDANDRITE - Danish Research Institute of Translational NeuroscienceDANDRITE - Danish Research Institute of Translational NeuroscienceSchool of Biosciences, Cardiff UniversityDANDRITE - Danish Research Institute of Translational NeuroscienceDepartment of Neuro- and Sensory Physiology, University Medical Center GöttingenBrain and Mind Centre & Faculty of Medicine and Health, School of Medical Sciences, University of SydneyDANDRITE - Danish Research Institute of Translational NeuroscienceAbstract 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.https://doi.org/10.1038/s41531-024-00841-9 |
| spellingShingle | Nanna Møller Jensen YuHong Fu Cristine Betzer Hongyun Li Sara Elfarrash Ali H. Shaib Donatus Krah Zagorka Vitic Lasse Reimer Hjalte Gram Vladimir Buchman Mark Denham Silvio O. Rizzoli Glenda M. Halliday Poul Henning Jensen MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity npj Parkinson's Disease |
| title | MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity |
| title_full | MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity |
| title_fullStr | MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity |
| title_full_unstemmed | MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity |
| title_short | MJF-14 proximity ligation assay detects early non-inclusion alpha-synuclein pathology with enhanced specificity and sensitivity |
| title_sort | mjf 14 proximity ligation assay detects early non inclusion alpha synuclein pathology with enhanced specificity and sensitivity |
| url | https://doi.org/10.1038/s41531-024-00841-9 |
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