The most common inherited cause of vascular dementia and stroke, cerebral autosomal dominant arteriopathy with subcortical infacts and leukoencephalopathy (CADASIL), is caused by mutations in NOTCH3. Post-translationally altered NOTCH3 accumulates in the vascular media of CADASIL arteries in areas of the vessels that exhibit profound cellular degeneration. The identification of molecules that concentrate in the same location as altered pathological NOTCH3 may shed light on process that drive cytopathology in CADASIL. We performed an immunohistochemical screen of markers identified in the Human Protein Atlas to identify new proteins that accumulate in the vascular media in a pattern similar to pathological NOTCH3. None of 16 smooth muscle cell markers exhibited NOTCH3-like patterns of expression, although several exhibited disease-dependent patterns of expression, with FAM124A, GZMM, MTFR1, and ST6GAL demonstrating higher expression in controls than CADASIL. In contrast, three non-smooth muscle proteins, CD63, CTSH, and IL17RC, localized to the same regions as pathological NOTCH3. Proximity ligation assays support complex formation between NOTCH3 fragments and CD63 in degenerating CADASIL media. The three novel CADASIL markers are preferentially expressed in perivascular cells in normal vessels, and mRNA encoding these molecules are expressed around the media in CADASIL. The identification of new proteins that concentrate in CADASIL vascular media demonstrates the utility of querying publicly available protein databases in specific neurological diseases and uncovers unexpected origins of vascular medial markers.