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Importantly, aggregated \u03b1-syn also accumulates in the cerebrospinal fluid (CSF) of PD patients, and while increasingly used for diagnosis, its pathological role remains poorly understood. Here, we demonstrate that \u03b1-syn accumulation in central nervous system (CNS) border tissues promotes CNS clearance deficits, as observed in PD patients. We find that aggregated \u03b1-syn accumulates not only in the CSF but also in the dura mater of individuals with PD, and, using acute and chronic mouse models, show that \u03b1-syn deposition in these sites induces immune alterations in CNS borders and disrupts CNS clearance. Mechanistically, we reveal that \u03b1-syn at CNS borders elevates CSF TNF and demonstrate that both TNF and \u03b1-syn aggregates themselves impair lymphatic endothelial cell function. These findings demonstrate a pathological role for \u03b1-syn in the CNS border tissues and position meningeal immunity as a contributor to CNS clearance deficits in PD pathogenesis.<\/jats:p>","DOI":"10.1084\/jem.20251245","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T13:55:00Z","timestamp":1792504500000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Cerebrospinal fluid and dural accumulation of \u03b1-synuclein impairs CNS clearance in Parkinson\u2019s disease"],"prefix":"10.1084","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6032-1445","authenticated-orcid":true,"given":"Taylor J.","family":"Stevenson","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03b94tp07","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Auckland 1 Department of Pharmacology and Clinical Pharmacology, , Auckland,","place":["New 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