AI Article Synopsis
- The MJF-14 PLA is a new technique for detecting α-synuclein aggregates, demonstrating high specificity and sensitivity for non-Lewy body pathology.
- This assay shows a strong correlation between α-synuclein aggregation and specific conditions in both cell cultures and human neuronal samples linked to neurodegenerative diseases.
- The findings indicate that a significant amount of α-synuclein pathology occurs before the formation of Lewy bodies in diseases such as Parkinson's, suggesting the need for further research using brain samples.
Article 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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607433 | PMC |
| http://dx.doi.org/10.1038/s41531-024-00841-9 | DOI Listing |
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