{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:06:52Z","timestamp":1784678812522,"version":"3.55.0"},"reference-count":69,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Parkinson's disease (PD) and multiple system atrophy are defined by \u03b1\u2010synuclein (\u03b1SYN)\u2010positive inclusions \u2013 Lewy bodies (LBs) and glial cytoplasmic inclusions \u2013 yet mounting evidence indicates that these inclusions represent only a fraction of disease\u2010relevant pathology. \u03b1SYN exists in dynamic conformational states, and soluble oligomeric assemblies, often undetectable by conventional immunohistochemistry, are increasingly implicated as key neurotoxic species. The \u03b1SYN proximity ligation assay (\u03b1SYN\u2010PLA) enables in situ detection of widespread non\u2010inclusion oligomeric pathology across synucleinopathies. Notably, PLA studies in\n                    <jats:italic>LRRK2<\/jats:italic>\n                    \u2010associated PD demonstrate abundant oligomeric \u03b1SYN even in cases lacking LBs, challenging the centrality of inclusions in defining disease. In this Perspective, we outline the principles of \u03b1SYN\u2010PLA, discuss antibody strategies and structural implications of detected species, review current evidence \u2013 including LB\u2010negative\n                    <jats:italic>LRRK2<\/jats:italic>\n                    \u2010PD \u2013 and consider temporal dynamics and clinical applications of PLA\u2010positive aggregates as biomarkers and therapeutic targets. \u00a9 2026 The Author(s).\n                    <jats:italic>Movement Disorders<\/jats:italic>\n                    published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                  <\/jats:p>","DOI":"10.1002\/mds.70335","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T02:39:25Z","timestamp":1777257565000},"page":"1680-1689","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Seeing Invisible Oligomers: Rethinking \u03b1\u2010Synuclein Pathology Through Proximity Ligation Assay"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9683-5966","authenticated-orcid":false,"given":"Hiroaki","family":"Sekiya","sequence":"first","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1177-5197","authenticated-orcid":false,"given":"Nanna M\u00f8ller","family":"Jensen","sequence":"additional","affiliation":[{"name":"DANDRITE \u2013 Danish Research Institute of Translational Neuroscience  Aarhus Denmark"},{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"},{"name":"PACE \u2013 Lundbeck Foundation Parkinson's Disease Research Center Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7189-7917","authenticated-orcid":false,"given":"Dennis W.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4439-9020","authenticated-orcid":false,"given":"Poul Henning","family":"Jensen","sequence":"additional","affiliation":[{"name":"DANDRITE \u2013 Danish Research Institute of Translational Neuroscience  Aarhus Denmark"},{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"},{"name":"PACE \u2013 Lundbeck Foundation Parkinson's Disease Research Center Aarhus University Hospital  Aarhus 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