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Diagnostic and prognostic performance of plasma neurofilament light chain in multiple system atrophy: a cross-sectional and longitudinal study

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Abstract

Background

The longitudinal dynamics of neurofilament light chain (NfL) in multiple system atrophy (MSA) were incompletely illuminated. This study aimed to explore whether the plasma NfL (pNfL) could serve as a potential biomarker of clinical diagnosis and disease progression for MSA.

Methods

We quantified pNfL concentrations in both a large cross-sectional cohort with 214 MSA individuals, 65 PD individuals, and 211 healthy controls (HC), and a longitudinal cohort of 84 MSA patients. Propensity score matching (PSM) was used to balance the age between the three groups. The pNfL levels between groups were compared using Kruskal–Wallis test. Linear mixed models were performed to explore the disease progression-associated factors in longitudinal MSA cohort. Random forest model as a complement to linear models was employed to quantify the importance of predictors.

Results

Before and after matching the age by PSM, the pNfL levels could reliably differentiate MSA from HC and PD groups, but only had mild potential to distinguish PD from HC. By combining linear and nonlinear models, we demonstrated that pNfL levels at baseline, rather than the change rate of pNfL, displayed potential prognostic value for progression of MSA. The combination of baseline pNfL levels and other modifiers, such as subtypes, Hoehn–Yahr stage at baseline, was first shown to improve the diagnosis accuracy.

Conclusions

Our study contributed to a better understanding of longitudinal dynamics of pNfL in MSA, and validated the values of pNfL as a non-invasive sensitive biomarker for the diagnosis and progression. The combination of pNfL and other factors is recommended for better monitoring and prediction of MSA progression.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank all of the participants for their involvement in this study.

Funding

This study was funded by the National Key R&D Program of China (No. 2021YFA0805200 to H Jiang), the National Natural Science Foundation of China (No. 81974176 and No. 82171254 to H Jiang; No.81901305 to C Wang), the Innovation Research Group Project of Natural Science Foundation of Hunan Province (No.2020JJ1008 to H Jiang), the Scientific Research Foundation of Health Commission of Hunan Province (No. B2019183 to H Jiang), the Key Research and Development Program of Hunan Province (No. 2020SK2064 to H Jiang), the Innovative Research and Development Program of Development and Reform Commission of Hunan Province to H Jiang, the Natural Science Foundation of Hunan Province (No. 2022JJ20094 and No.2021JJ40974 to Z Chen; No.2020JJ5925 to C Wang; No.2022JJ40783 to L He), the Central South University Research Programme of Advanced Interdisciplinary Study (No. 2023QYJC010 to H Jiang), the Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital, No.2020LNJJ12 to H Jiang), the Science and Technology Innovation Program of Hunan Province (2022RC1027 to Z Chen).

Author information

Author notes

  1. Linliu Peng, Linlin Wan and Mingjie Liu have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Linliu Peng, Linlin Wan, Mingjie Liu, Daji Chen, Xinrong Yuan, Zhichao Tang, You Fu, Sudan Zhu, Lijing Lei, Huirong Peng, Yuting Shi, Hongyu Yuan, Na Wan, Xuan Hou, Beisha Tang, Zhao Chen & Hong Jiang

  2. Department of Neurology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China

    Hong Jiang

  3. Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, 410008, Hunan, China

    Linlin Wan, Jinchen Li, Beisha Tang, Zhao Chen & Hong Jiang

  4. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Jinchen Li, Beisha Tang, Zhao Chen & Hong Jiang

  5. Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Linlin Wan

  6. Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China

    Beisha Tang, Zhao Chen & Hong Jiang

  7. School of Computer Science and Engineering, Central South University, Changsha, 410083, Hunan, China

    Rong Qiu

  8. Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China

    Zhe Long

  9. Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Chunrong Wang & Lang He

  10. Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008, Hunan, China

    Kun Xia & Chao Chen

  11. Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, 410008, Hunan, China

    Kun Xia & Chao Chen

  12. National International Collaborative Research Center for Medical Metabolomics, Central South University, Changsha, 410008, Hunan, China

    Linlin Wan & Hong Jiang

  13. Department of Neurology, the Affiliated Nanhua Hospital, University of South China, Hengyang, 421002, Hunan, China

    Mingjie Liu

Authors
  1. Linliu Peng
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  2. Linlin Wan
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  3. Mingjie Liu
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  4. Zhe Long
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  5. Daji Chen
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  6. Xinrong Yuan
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  7. Zhichao Tang
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  8. You Fu
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  9. Sudan Zhu
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  10. Lijing Lei
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  11. Chunrong Wang
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  12. Huirong Peng
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  13. Yuting Shi
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  14. Lang He
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  15. Hongyu Yuan
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  16. Na Wan
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  17. Xuan Hou
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  18. Kun Xia
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  19. Jinchen Li
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  20. Chao Chen
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  21. Rong Qiu
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  22. Beisha Tang
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  23. Zhao Chen
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  24. Hong Jiang
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Contributions

Conceptualization: LLP, LLW, MJL, ZC, BST and HJ; methodology: LLP, LLW and MJL; formal analysis and investigation: LLP, LLW, MJL, ZL, DJC, XRY, ZCT, YF, SDZ, LJL, CRW, HRP, YTS, LH, HYY, NW, XH, KX, JCL, CC, RQ, ZC and HJ; writing—original draft preparation: LLP and LLW; writing—review and editing: ZC, BST and HJ; funding acquisition: ZC, CRW, LH and HJ.

Corresponding authors

Correspondence to Zhao Chen or Hong Jiang.

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Conflicts of interest

The authors declare that they have no conflict of interest.

Ethics statement

This present study was approved by the Ethics Committee of Xiangya Hospital, Central South University and written informed consent was obtained from all participants.

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Peng, L., Wan, L., Liu, M. et al. Diagnostic and prognostic performance of plasma neurofilament light chain in multiple system atrophy: a cross-sectional and longitudinal study. J Neurol 270, 4248–4261 (2023). https://doi.org/10.1007/s00415-023-11741-y

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  • DOI: https://doi.org/10.1007/s00415-023-11741-y

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