ABCD1 dysfunction alters white matter microvascular perfusion

Arne Lauer, Xiao Da, Mikkel Bo Hansen, Gregoire Boulouis, Yangming Ou, Xuezhu Cai, Afonso Liberato Celso Pedrotti, Jayashree Kalpathy-Cramer, Paul Caruso, Douglas L. Hayden, Natalia Rost, Kim Mouridsen, Florian S. Eichler, Bruce Rosen, Patricia L. Musolino

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Cerebral X-linked adrenoleukodystrophy is a devastating neurodegenerative disorder caused by mutations in the ABCD1 gene, which lead to a rapidly progressive cerebral inflammatory demyelination in up to 60% of affected males. Selective brain endothelial dysfunction and increased permeability of the blood-brain barrier suggest that white matter microvascular dysfunction contributes to the conversion to cerebral disease. Applying a vascular model to conventional dynamic susceptibility contrast magnetic resonance perfusion imaging, we demonstrate that lack of ABCD1 function causes increased capillary flow heterogeneity in asymptomatic hemizygotes predominantly in the white matter regions and developmental stages with the highest probability for conversion to cerebral disease. In subjects with ongoing inflammatory demyelination we observed a sequence of increased capillary flow heterogeneity followed by blood-brain barrier permeability changes in the perilesional white matter, which predicts lesion progression. These white matter microvascular alterations normalize within 1 year after treatment with haematopoietic stem cell transplantation. For the first time in vivo, our studies unveil a model to assess how ABCD1 alters white matter microvascular function and explores its potential as an earlier biomarker for monitoring disease progression and response to treatment.

Original languageEnglish (US)
Pages (from-to)3139-3152
Number of pages14
Issue number12
StatePublished - Dec 1 2017


  • ABCD1
  • ALD
  • cerebral X-linked adrenoleukodystrophy
  • inflammatory demyelination
  • microvascular perfusion

ASJC Scopus subject areas

  • Clinical Neurology


Dive into the research topics of 'ABCD1 dysfunction alters white matter microvascular perfusion'. Together they form a unique fingerprint.

Cite this