Objective: This study aims to determine the Neurofilament light chain (NfL) expression in oligodendrocytes, investigate whether excess α-synuclein (α-syn) impacts NfL expression, release, and functions in oligodendrocytes, as well as detect plasma NfL-positive oligodendrocyte-derived extracellular vesicles (ODEVs) changes in patients with multiple system atrophy (MSA), Parkinson’s disease (PD), and healthy controls (HCs).
Background: NfL levels in cerebrospinal fluid and blood are higher in MSA than in PD. The reason for these differences remains unclear but might be attributed to the differences in α-syn accumulation in neurons or oligodendrocytes. However, the understanding of NfL presence and release in oligodendrocytes is limited.
Method: 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-cells. The MO3.13 oligodendrocyte cell line was used to mimic MSA pathology with α-syn 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-positive ODEVs were quantified using nano-scale flow cytometry in a cohort of 101 MSA patients, 96 PD patients, and 97 HCs.
Results: Both NEFL mRNA and NfL protein showed co-localization with typical oligodendrocyte marker CNPase. 58.5% of CNPase-positive oligodendrocytes co-expressed NfL. Increased α-syn load elevates NfL expression in both oligodendrocyte cell line and MSA patient brain slices. NfL overexpression inhibited oligodendrocyte maturation but did not affect α-syn-induced cell viability deficits. α-Syn promoted oligodendrocytic NfL release via EVs. Plasma NfL-positive ODEVs were elevated in MSA patients compared to PD and HCs.
Conclusion: 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.
To cite this abstract in AMA style:
YC. Zheng, WY. Kou, GX. Yang, HH. Cai, C. Yang, SM. Li, BX. Zhu, JY. Wu, Y. Huang, ZW. Yu, T. Feng. Alpha-Synuclein Promotes the Expression and Release of Neurofilament Light Chain from Oligodendrocytes in Multiple System Atrophy [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/alpha-synuclein-promotes-the-expression-and-release-of-neurofilament-light-chain-from-oligodendrocytes-in-multiple-system-atrophy/. Accessed November 20, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/alpha-synuclein-promotes-the-expression-and-release-of-neurofilament-light-chain-from-oligodendrocytes-in-multiple-system-atrophy/