Recently, proteomic studies on cerebral amyloid angiopathy (CAA), a common cause of age-related dementia, and cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most prevalent monogenic small-vessel disease, have provided evidence for an impairment of HTRA1 activity through sequestration into pathological protein deposits, suggesting an alternative mechanism of HTRA1 inactivation and expanding the range of diseases with HTRA1 involvement. This evidence concerns the gene HTRA1 and CADASIL.