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This study aims to determine the NfL expression in oligodendrocytes, investigate whether excess \u0251\u2010synuclein (\u03b1\u2010syn) impacts NfL expression, release, and functions in oligodendrocytes, as well as detect plasma NfL\u2010positive oligodendrocyte\u2010derived extracellular vesicles (ODEVs) changes in patients with multiple system atrophy (MSA), Parkinson's disease (PD), and healthy controls (HCs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>NfL expression in oligodendrocytes was assessed using RNAscope and immunofluorescence staining in human and mouse brain slices, as well as flow cytometry in mouse brain single\u2010cells. The MO3.13 oligodendrocyte cell line was used to mimic MSA pathology with \u03b1\u2010syn overexpression or preformed fibril treatment. NfL levels were detected in cell line, brain tissues and condition media, and the differences between MSA pathology and controls were compared. Plasma NfL\u2010positive ODEVs were quantified using nano\u2010scale flow cytometry in a cohort of 101 MSA patients, 96 PD patients, and 97 HCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both\n                      <jats:italic>NEFL<\/jats:italic>\n                      mRNA and NfL protein showed co\u2010localization with typical oligodendrocyte marker anti\u20102,3\u2010cyclic nucleotide\u20103\u2010phosphodiesterase (CNPase). A total of 58.5% of CNPase\u2010positive oligodendrocytes co\u2010expressed NfL. Increased \u03b1\u2010syn load elevates NfL expression in both oligodendrocyte cell line and MSA patient brain slices. NfL overexpression inhibited oligodendrocyte maturation, but did not affect \u03b1\u2010syn\u2010induced cell viability deficits. \u03b1\u2010Syn promoted oligodendrocytic NfL release via extracellular vesicles. Plasma NfL\u2010positive ODEVs were elevated in MSA patients compared to PD and HCs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>These findings suggest additional cellular roles for NfL in oligodendrocytes beyond its established function in neurons and have potential implications for the neurodegenerative pathophysiology of MSA. ANN NEUROL 2025;98:1364\u20131379<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.70029","type":"journal-article","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T07:18:34Z","timestamp":1754723914000},"page":"1364-1379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["\u03b1\u2010Synuclein Promotes the Expression and Release of Neurofilament Light Chain from Oligodendrocytes in a Murine Model: Implication for Multiple System Atrophy?"],"prefix":"10.1002","volume":"98","author":[{"given":"Yuanchu","family":"Zheng","sequence":"first","affiliation":[{"name":"Center for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University  Beijing China"},{"name":"China National Clinical Research Center for Neurological Diseases  Beijing 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