Pathogenesis of Small vessel Disease of the Brain

European Coordinator:
  • Anne JOUTEL, INSERM, Université Paris 7- Denis Diderot (France)
North American Coordinator:
  • Mark T. NELSON, University of Vermont, Burlington (USA)
Members:
  • Cenk AYATA, Massachusetts General Hospital, Harvard Medical School, Charlestown (USA)
  • Hugues CHABRIAT, University Paris 7-Denis Diderot, Paris (France)
  • Martin DICHGANS, University of München (Germany)
  • Frank FARACI, University of Iowa City (USA)
  • Christophe TZOURIO, INSERM, Bordeaux (France)
  • Stephanie DEBETTE, University of Bordeaux and Paris7-Denis Diderot (France)
  • Maïken NEDERGAARD, University of Rochester Medical School (USA)
  • Nikolaus PLESNILA, University of München (Germany)

Small vessel disease (SVD) involving the structure and function of small penetrating vessels within the brain accounts for 25% to 30% of ischemic strokes and is a leading cause of cognitive decline and disability worldwide. Very little is known about the underlying causes of SVD.  There are currently no specific treatments, and therapeutic options for secondary prevention are particularly limited compared to other common causes of stroke. The identification of genes involved in two genetic forms of non-hypertensive adult-onset SVD marks an important advance in the understanding of SVD.

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is an archetypal SVD that emerges as the most common heritable cause of stroke and vascular dementia worldwide.  CARASIL (Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), predominantly reported in Japanese families, is a rare SVD with a more complex phenotype.  This Transatlantic Network of Excellence aims to use unique mouse models of CADASIL and CARASIL as a basis to explore common forms of SVD, and ultimately to identify potential therapeutic targets.   In addition, there is considerable emphasis placed on training the next generation of investigators in this nascent field.