{"doi":"10.1038/s41531-024-00841-9","title":"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 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.","journal":"npj Parkinson s Disease","year":2024,"id":426272,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":668237,"name":"YuHong Fu","orcid":"0000-0003-4539-2039","position":1,"is_corresponding":false},{"id":642148,"name":"Cristine Betzer","orcid":"0000-0001-5429-3548","position":2,"is_corresponding":false},{"id":864354,"name":"Hongyun Li","orcid":"0000-0003-3332-3132","position":3,"is_corresponding":false},{"id":1225168,"name":"Sara Elfarrash","orcid":"0000-0002-4573-3131","position":4,"is_corresponding":false},{"id":1225169,"name":"Ali H. Shaib","orcid":"0009-0007-2656-3820","position":5,"is_corresponding":false},{"id":1204621,"name":"Donatus Krah","orcid":"0009-0003-1151-7726","position":6,"is_corresponding":false},{"id":1225170,"name":"Zagorka Vitic","orcid":"0009-0002-5129-841X","position":7,"is_corresponding":false},{"id":642147,"name":"Lasse Reimer","orcid":"0000-0002-6996-3185","position":8,"is_corresponding":false},{"id":642144,"name":"Hjalte Gram","orcid":"0000-0001-6516-5189","position":9,"is_corresponding":false},{"id":455043,"name":"Vladimir L. Buchman","orcid":"0000-0002-7631-8352","position":10,"is_corresponding":false},{"id":1225171,"name":"Mark Denham","orcid":"0000-0001-5279-5915","position":11,"is_corresponding":false},{"id":647722,"name":"Silvio O. Rizzoli","orcid":"0000-0002-1667-7839","position":12,"is_corresponding":false},{"id":291678,"name":"Glenda M. Halliday","orcid":"0000-0003-0422-8398","position":13,"is_corresponding":false},{"id":625539,"name":"Poul Henning Jensen","orcid":"0000-0002-4439-9020","position":14,"is_corresponding":false},{"id":920740,"name":"Nanna Møller Jensen","orcid":"0000-0003-1177-5197","position":0,"is_corresponding":true}],"reference_count":132,"raw_metadata":null,"created_at":"2026-07-19T01:58:37.924718Z","pmid":"39613827","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}