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Diffusion MRI Captures White Matter Microstructure Alterations in PRKN Disease.

Takahiro Koinuma1, Taku Hatano1, Koji Kamagata2

  • 1Department of Neurology, Faculty of Medicine, Juntendo University, Tokyo, Japan.

Journal of Parkinson'S Disease
|April 26, 2021
PubMed
Summary

Parkinson's disease (PD) patients with parkin (PRKN) mutations show white matter (WM) microstructural damage. This damage correlates with disease duration and oxidative stress markers, suggesting PRKN's role in WM integrity.

Keywords:
Diffusion MRIParkinson’s diseasemagnetic resonance imaging (MRI)metabolomicsoxidative stress

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Area of Science:

  • Neuroscience
  • Neurology
  • Radiology

Background:

  • Pathological studies of parkin (PRKN) mutations in Parkinson's disease (PD) typically focus on dopaminergic neurons, with limited understanding of white matter (WM) pathology.
  • Previous research linked idiopathic PD to WM microstructural alterations via oxidative stress, and PRKN patients exhibit similar oxidative stress biomarkers.
  • This suggests a potential role for PRKN mutations in causing WM abnormalities.

Purpose of the Study:

  • To investigate white matter (WM) microstructural abnormalities in early-onset Parkinson's disease (PD) patients with parkin (PRKN) mutations.
  • To utilize diffusion tensor imaging (DTI) to assess WM integrity in PRKN mutation carriers.

Main Methods:

  • Recruited nine PRKN patients and 15 healthy controls.
  • Acquired diffusion MRI data using a 3T scanner with specific DTI parameters (b-value 1,000 s/mm², 32 gradients).
  • Analyzed DTI measures using tract-based spatial statistics (TBSS) and correlated findings with serum oxidative stress markers.

Main Results:

  • While total WM volume was unchanged, PRKN patients showed decreased fractional anisotropy and increased mean and radial diffusivity in specific WM tracts (corona radiata, uncinate fasciculus).
  • These DTI changes indicate microstructural impairments in the white matter of PRKN patients.
  • Serum oxidative stress markers (9-hydroxystearate) and disease duration positively correlated with DTI parameters.

Conclusions:

  • This pilot study indicates that white matter (WM) microstructural impairments are present in patients with parkin (PRKN) mutations.
  • These WM abnormalities are associated with both disease duration and systemic oxidative stress.
  • The findings suggest PRKN plays a role in maintaining white matter integrity.