Correspondence between the molecular genetic analysis and electron microscopic detection of granular osmiophilic material in CADASIL

Abstract

Background and aims: CADASIL is the most common hereditary vascular dementia. It is caused by mutations in NOTCH3 gene (>150 different) encoding transmembrane receptor Notch3. The main pathological findings are thick fibrotic arterial walls and accumulation of Notch3 extracellular domain (N3ECD) at degenerating VSMCs. In electron microscopy (EM) the pathognomonic feature is accumulation of granular osmiophilic material (GOM) in indentations of VSMCs or in the extracellular space next to VSMCs. GOM has been considered a specific diagnostic marker of CADASIL.