As a model mechanism of action, one of the pathophysiological markers of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) and mutations in the NOTCH3 gene includes an increase in WMHs and a loss of vascular smooth muscle cells.66 The gene discussed is NOTCH3; the disease is cerebral arteriopathy with subcortical infarcts and leukoencephalopathy.