Serum Neurofilament Light Chain and GFAP Levels Are Associated with Structural Brain Connectivity in Parkinson's Disease.

Overview

1. Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy; (M.C.B.); (J.B.); (C.C.); (M.G.B.); (C.M.C.); (A.Q.)
2. Neuroscience Research Center, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
3. Institute of Neurology, Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy
4. Diffusion Imaging and Connectivity Estimation (DICE) Lab, Department of Computer Science, University of Verona, 37129 Verona, Italy; (M.B.); (A.D.)
5. Department of Engineering for Innovation Medicine, University of Verona, 37129 Verona, Italy

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms and widespread alterations in brain networks. Circulating biomarkers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) reflect neuroaxonal damage and astroglial activation, respectively, but their relationship with large-scale brain connectivity remains poorly understood. Seventy-three PD patients and thirty-four healthy controls underwent diffusion magnetic resonance imaging. Whole-brain tractography was used to reconstruct structural connectivity networks, and graph-theoretical measures were derived. Serum NfL and GFAP levels were quantified, and their associations with network metrics and clinical variables were assessed. PD patients showed significant alterations in global and nodal network organization compared to controls. Higher NfL and GFAP levels were associated with reduced global clustering coefficient and efficiency, as well as increased path length and modularity. At the regional level, higher biomarker levels were associated with reduced network measures in the right thalamus and right cerebellar cortex. No significant associations were observed in healthy controls. These findings demonstrate that circulating biomarkers of neurodegeneration are linked to both global and regional disruptions of structural brain connectivity in PD, supporting the integration of blood-based biomarkers and connectomics to better characterize disease-related network alterations.

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Data Availability Statement

The data presented in this study are available on reasonable request from the corresponding author due to privacy restrictions.

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 5 keywords, 12 MeSH terms, 1 funder, 62 references.

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This paper

Bonacci, M. C., Buonocore, J., Calomino, C., Bianco, M. G., Battocchio, M., Bontempi, P., Daducci, A., Cristiani, C. M., Quattrone, A., Caligiuri, M. E., & Quattrone, A. (2026). Serum Neurofilament Light Chain and GFAP Levels Are Associated with Structural Brain Connectivity in Parkinson's Disease. International journal of molecular sciences, 27(9), 3934. https://doi.org/10.3390/ijms27093934

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