Abstract
Cerebrospinal fluid (CSF) flow dynamics play a critical role in clearing pathological proteins from the brain, which may potentially influence the progression of neurodegenerative diseases. We aimed to investigate the alterations of CSF flow dynamics in patients with Parkinson’s disease (PD). We employed the multiple low b-values diffusion magnetic resonance imaging combined with CSF-based spatial statistics to evaluate changes of CSF pseudo-diffusivity within ventricles, sulci, and cisterns in PD. We assessed the relationships between CSF pseudo-diffusivity and other indirect markers of glymphatic system, including the diffusion-tensor imaging along the perivascular space (DTI-ALPS) index, the volume of the choroid plexus and perivascular spaces. We explored the association between CSF pseudo-diffusivity and the integrity of the locus coeruleus (LC). A total of 44 patients and 48 healthy controls participated in the study. PD patients showed significantly reduced CSF pseudo-diffusivity within the ventricles and sulci, with no significant changes within the cisterns. Lower CSF pseudo-diffusivity was correlated with lower DTI-ALPS index. Furthermore, decreased CSF pseudo-diffusivity was correlated with LC degeneration. These findings suggested that PD exhibit reduced CSF flow dynamics within the ventricles and sulci. Furthermore, LC-norepinephrine system dysfunction may represent a potential mechanism and target for modulating CSF flow dynamics.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Code availability
The source code for CBSS processing is provided in https://github.com/Yutong441/CBSS.
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Acknowledgements
We thank Shanghai Tengyun Biotechnology Co., Ltd for developing Hiplot Pro platform (https://hiplot.com.cn/) and providing valuable tools for data analysis and visualization. Hiplot is a free tool and none of the authors have any financial interests or relationships to disclose that could inappropriately influence, or be perceived to influence, the work presented in this manuscript. This work was supported by the National Natural Science Foundation of China (Grant Nos. 82302132, 82271935, 82171888, 82202091, 82001767, 91630314, 82071997, 82302136, 82202089, 82371906, 82302135, and 81971577), the Natural Science Foundation of Zhejiang Province (Grant No. LY22H180002, LQ21H180008, and Z24H180002), the 13th Five-year Plan for National Key Research and Development Program of China (Grant No. 2016YFC1306600), and the China Postdoctoral Science Foundation (2023M733085).
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M.Z. has full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: C.Z., H.H., and M.Z. Acquisition, analysis, or interpretation of data: C.Z., X.G., T.G., and X.X. Drafting of the manuscript: C.Z. Critical review of the manuscript for important intellectual content: All authors. Statistical analysis: C.Z., H.H., and Y.C. Obtained funding: M.Z., C.Z., X.G., T.G., and X.X. Administrative, technical, or material support: M.Z. Supervision: M.Z.
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Zhou, C., Hong, H., Chen, Y. et al. Alterations of cerebrospinal fluid flow dynamics in Parkinson’s disease. npj Parkinsons Dis. (2026). https://doi.org/10.1038/s41531-025-01257-9
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DOI: https://doi.org/10.1038/s41531-025-01257-9
