Specific Aims

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 CBF, autoregulation, NVC, and susceptibility to cortical spreading depression (CSD) contribute to long- term pathological consequences. Our Overall Objective is to identify therapeutic targets for the treatment of SVD.

Aim 1: To identify the network of genes/gene products that drive small vessel pathology in CADASIL and CARASIL.


Aim 2: To elucidate the mechanisms linking Notch3 and HtrA1 mutations to the functional deficits and brain pathology in CADASIL and CARASIL.


Aim 3: To assess the contribution of genes of the CADASIL and CARASIL disease pathways to common non-Mendelian SVD.