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April 3, 2026Movement Disorders

Divergent Glymphatic Dysfunction and Free Water Pathology Underpin Distinct Mechanisms and Enable Differential Diagnosis in Parkinson's Disease and Multiple System Atrophy

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Authors

RSRuinan ShenZMZexuan MengXZXue Zhu

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Overview

Cross-sectional and longitudinal neuroimaging analyses reveal distinct biomarkers for Parkinson's and MSA, suggesting new diagnostic approaches.

Key Points

  • Evaluate glymphatic function and free water pathology in Parkinson's disease and multiple system atrophy to identify differential diagnostic biomarkers.
  • Conducted a cross-sectional and longitudinal neuroimaging study with 231 participants including healthy controls, PD, and MSA patients.
  • Analyzed glymphatic function using diffusion tensor imaging and choroid plexus volume metrics from MRI scans.
  • Evaluated diagnostic performance with receiver operating characteristic curves and performed mediation analyses.
  • Both PD and MSA showed reduced glymphatic function and expanded choroid plexus volume compared to healthy controls.
  • Free water accumulation patterns differed: cortical/midline in PD and cerebellar in MSA.
  • Longitudinal studies indicated progressive free water accumulation in specific regions.
  • Strong coupling between glymphatic dysfunction and free water was evident in PD but absent in MSA.
  • An integrated model combining imaging and clinical metrics demonstrated high diagnostic accuracy with an area under the curve of 0.994.

Cite This Study

Shen et al. (2026) studied this question.

synapsesocial.com/papers/69cf5cb15a333a821460a35ehttps://doi.org/10.1002/mds.70293
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