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. 2024 Oct;271(10):6991-6999.
doi: 10.1007/s00415-024-12647-z. Epub 2024 Sep 10.

GFAP and NfL as fluid biomarkers for clinical disease severity and disease progression in multiple system atrophy (MSA)

Sabrina Katzdobler  1   2   3   4 , Georg Nübling  1   3 , Martin Klietz  5 , Urban M Fietzek  1   3 , Carla Palleis  1   2   3 , Alexander M Bernhardt  1   3   6 , Florian Wegner  5 , Meret Huber  5 , Sophia Rogozinski  5 , Luisa-Sophie Schneider  7 , Eike Jakob Spruth  8   9 , Aline Beyle  10 , Ina R Vogt  11 , Moritz Brandt  12   13 , Niels Hansen  14 , Wenzel Glanz  15   16   17 , Kathrin Brockmann  18   19 , Annika Spottke  10   11 , Daniel C Hoffmann  11 , Oliver Peters  7   8 , Josef Priller  20   21   22 , Jens Wiltfang  14   23   24 , Emrah Düzel  15   16   25 , Anja Schneider  11   26 , Björn Falkenburger  12   13 , Thomas Klockgether  10   11 , Thomas Gasser  18   19 , Brigitte Nuscher  27 , Christian Haass  2   3   27 , Günter Höglinger  28   29   30 , Johannes Levin  31   32   33   34   35
Affiliations

GFAP and NfL as fluid biomarkers for clinical disease severity and disease progression in multiple system atrophy (MSA)

Sabrina Katzdobler et al. J Neurol. 2024 Oct.

Abstract

Background: Multiple system atrophy (MSA), an atypical parkinsonian syndrome, is a rapidly progressive neurodegenerative disease with currently no established fluid biomarkers available. MSA is characterized by an oligodendroglial α-synucleinopathy, progressive neuronal cell loss and concomitant astrocytosis. Here, we investigate glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as fluid biomarkers for differential diagnosis, assessment of clinical disease severity and prediction of disease progression in MSA.

Methods: GFAP and NfL levels were analyzed in plasma and CSF samples of 47 MSA patients as well as 24 Parkinson's disease (PD) and 25 healthy controls (HC) as reference cohorts. In MSA, biomarker levels were correlated to baseline and longitudinal clinical disease severity (UMSARS scores).

Results: In MSA, GFAP levels in CSF and plasma predicted baseline clinical disease severity as indicated by UMSARS scores, while NfL levels predicted clinical disease progression as indicated by longitudinal changes in UMSARS scores. Cross-sectionally, NfL levels in CSF and plasma were significantly elevated in MSA compared to both PD and HC. Receiver operating curves (ROC) indicated high diagnostic accuracy of NfL for distinguishing MSA from PD (CSF: AUC = 0.97, 95% CI 0.90-1.00; plasma: AUC = 0.90, 95% CI 0.81-1.00).

Discussion: In MSA, GFAP shows promise as novel biomarker for assessing current clinical disease severity, while NfL might serve as biomarker for prediction of disease progression and differential diagnosis of MSA against PD.

Keywords: Fluid biomarkers; Glial fibrillary acidic protein; Multiple system atrophy; Neurofilament light chain; Neuroinflammation.

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Conflict of interest statement

The research in this study was funded by the Lüneburg heritage, the Ehrmann foundation and the Deutsche Forschungsgemeinschaft (DFG) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy—ID 390857198). The authors declare that there are no conflicts of interest relevant to this work.

Figures

Fig. 1
Fig. 1
NfL and GFAP as biomarkers in MSA, PD and HC. A Biomarkers for differential diagnosis. NfL levels are significantly increased in both CSF and plasma of MSA compared to PD and HC. GFAP levels in CSF are significantly higher in MSA compared to HC. ****p < 0.0001. No significant changes in GFAP plasma levels were observed between the three groups. B Receiver operating characteristic (ROC) curve analysis for NfL in CSF and plasma show high AUC values for discrimination of MSA from PD patients (CSF: AUC = 0.97; plasma: AUC = 0.90)
Fig. 2
Fig. 2
Biomarkers for clinical disease severity in MSA. CSF and plasma levels of GFAP and NfL in MSA compared to UMSARS I + II scores. Multiple regression analysis adjusting for age-identified GFAP levels in CSF and plasma as significant predictor of baseline UMSARS I + II scores in MSA patients, but not NfL
Fig. 3
Fig. 3
Biomarkers for prediction of disease progression in MSA. While no correlation was found for baseline levels of GFAP with longitudinal change in UMSARS scores over 12 months, CSF and plasma levels of NfL show significant positive correlation with longitudinal change in UMSARS scores over 12 months in MSA patients, indicating prediction of disease progression
See this image and copyright information in PMC

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