Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Stefanie Schreiber, Jose Bernal, Philipp Arndt, Frank Schreiber, Patrick Müller, Lorena Morton, Rüdiger Christian Braun-Dullaeus, Maria Del Carmen Valdés-Hernández, Roberto Duarte, Joanna Marguerite Wardlaw, Sven Günther Meuth, Grazia Mietzner, Stefan Vielhaber, Ildiko Rita Dunay, Alexander Dityatev, Solveig Jandke, Hendrik Mattern

Research output: Contribution to journalReview articlepeer-review

Abstract / Description of output

Brain vascular health appears to be critical for preventing the development of amyotrophic lateral sclerosis (ALS) and slowing its progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in their small cerebral blood vessels. Impaired vascular brain health has detrimental effects on motor neurons: vascular endothelial growth factor levels are lowered in ALS, which can compromise endothelial cell formation and the integrity of the blood-brain barrier. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.

Original languageEnglish
Issue number6
Publication statusPublished - 21 Mar 2023

Keywords / Materials (for Non-textual outputs)

  • Humans
  • Amyotrophic Lateral Sclerosis/metabolism
  • Motor Cortex/metabolism
  • Vascular Endothelial Growth Factor A/metabolism
  • Motor Neurons/pathology
  • Blood-Brain Barrier/pathology


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