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Neurofilament light chain in spinal fluid and plasma in multiple system atrophy: a prospective, longitudinal biomarker study

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Abstract

Purpose

There is a critical need for reliable diagnostic biomarkers as well as surrogate markers of disease progression in multiple system atrophy (MSA). Neurofilament light chain (NfL) has been reported to potentially meet those needs. We therefore sought to explore the value of NfL in plasma (NfL-p) in contrast to cerebrospinal fluid (NfL-c) as a diagnostic marker of MSA, and to assess NfL-p and NfL-c as markers of clinical disease progression.

Methods

Well-characterized patients with early MSA (n = 32), Parkinson’s disease (PD; n = 21), and matched controls (CON; n = 15) were enrolled in a prospective, longitudinal study of synucleinopathies with serial annual evaluations. NfL was measured using a high-sensitivity immunoassay, and findings were assessed by disease category and relationship with clinical measures of disease progression.

Results

Measurements of NfL-c were highly reproducible across immunoassay platforms (Pearson, r = 0.99), while correlation between NfL-c and -p was only moderate (r = 0.66). NfL was significantly higher in MSA compared with CON and PD; the separation was essentially perfect for NfL-c, but there was overlap, particularly with PD, for NfL-p. While clinical measures of disease severity progressively increased over time, NfL-c and -p remained at stable elevated levels within subjects across serial measurements. Neither change in NfL nor baseline NfL were significantly associated with changes in clinical markers of disease severity.

Conclusions

These findings confirm NfL-c as a faithful diagnostic marker of MSA, while NfL-p showed less robust diagnostic value. The significant NfL elevation in MSA was found to be remarkably stable over time and was not predictive of clinical disease progression.

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Acknowledgements

This publication was made possible by the National Institutes of Health (NIH; R01 NS092625, U19 AG71754, UL1 TR000135), the Food and Drug Administration (FDA) (R01 FD07290), grants from the Michael J. Fox Foundation for Parkinson’s Research, Sturm Foundation, Bishop Dr. Karl Golser Foundation, Mayo Center of Regenerative Medicine, and Mayo Funds. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH or FDA.

Funding

NIH, FDA, grants from the Michael J. Fox Foundation for Parkinson’s disease, Sturm Foundation, Bishop Dr. Karl Golser Foundation, Mayo Center of Regenerative Medicine, and Mayo Funds.

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Authors and Affiliations

  1. Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Wolfgang Singer, Ann M. Schmeichel, David M. Sletten, Tonette L. Gehrking, Jade A. Gehrking, Mariana D. Suarez, Jennifer K. Anderson, Pamela H. Bass & Phillip A. Low

  2. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Jorge Trejo-Lopez

  3. Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA

    Timothy G. Lesnick

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  1. Wolfgang Singer
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  2. Ann M. Schmeichel
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Contributions

WS and PL contributed to the conception and design of the study. WS, AS, DS, TG, JG, MS, JA, PB, and TL contributed to the acquisition and analysis of data. WS and DS contributed to drafting the text and preparing the figures.

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Correspondence to Wolfgang Singer.

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Singer, W., Schmeichel, A.M., Sletten, D.M. et al. Neurofilament light chain in spinal fluid and plasma in multiple system atrophy: a prospective, longitudinal biomarker study. Clin Auton Res 33, 635–645 (2023). https://doi.org/10.1007/s10286-023-00974-6

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  • DOI: https://doi.org/10.1007/s10286-023-00974-6

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