- Specific Aims
- CADASIL/CARASIL: GOM proteome, altered expression of Notch3 targets, and vascular functional deficits
- From monogenic to common SVD
- Network of genes/proteins driving vessel pathology in CADASIL/CARASIL
- Mechanisms underlying functional deficits and brain pathology in CADASIL/CARASIL
- Significance of CADASIL/CARASIL-related genes/proteins and disease pathways for common SVD
Our overarching hypothesis is that genes encoding the critical pathways underlying CADASIL and CARASIL contribute to the risk of sporadic SVD. We propose that functional defects in resting cerebral blood flow, autoregulation, neurovascular coupling, and susceptibility to cortical spreading depression (CSD) contribute to long-term pathological consequences.