CADASIL, the most frequent and intensely studied monogenic SVD, is characterized by a severe pathology in the cerebral vasculature including the mutation-induced aggregation of the Notch3 extracellular domain (Notch3ECD) and the formation of protein deposits of insufficiently determined composition in the extracellular space of vessel walls. To advance our understanding of protein accumulation in CADASIL-affected tissue, we quantitatively determined the proteome of cerebral vessels isolated from patient and control autopsy samples (n = 6 for each group), obtaining 95 proteins with significantly increased abundance.