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Cortical Pathology in Vanishing White Matter.

Jodie H K Man1,2,3, Charlotte A G H van Gelder4,5, Marjolein Breur1,2,3

  • 1Department of Child Neurology, Emma Children's Hospital, Amsterdam University Medical Centers, VU University Amsterdam, 1081 HV Amsterdam, The Netherlands.

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Vanishing white matter (VWM) involves cortical astrocytes, showing altered metabolism and morphology. This finding is crucial for developing new VWM therapies targeting brain cortex.

Keywords:
astrocytesastrocytopathycortexleukodystrophyproteomicsvanishing white matter

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Vanishing white matter (VWM) is a leukodystrophy primarily affecting white matter.
  • Cortical thinning is observed in long-term VWM patients, but direct cortical involvement is not well understood.
  • Astrocytes are implicated as key players in VWM pathogenesis.

Purpose of the Study:

  • To comprehensively analyze the VWM cortex at a molecular level.
  • To investigate potential disease mechanisms in VWM cortical involvement.
  • To understand the role of astrocytes in the VWM brain cortex.

Main Methods:

  • High-resolution mass-spectrometry-based proteomics.
  • Immunohistochemistry.
  • Gene ontology analysis.

Main Results:

  • 268 differentially expressed proteins identified in VWM cortices.
  • Proteins involved in cellular metabolism, especially mitochondrial activity, were enriched.
  • Cortical astrocytes in VWM patients showed morphological changes, reduced complexity, and immaturity.

Conclusions:

  • Cortical astrocytes are involved in VWM pathogenesis.
  • Altered cellular metabolism and astrocyte morphology are key features of VWM cortical changes.
  • These findings are critical for developing future therapeutic strategies for VWM.