Figure 1.

Differences and similarities between cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and cerebral amyloid angiopathy (CAA) histopathology and protein profiles. A: The histopathologies of CADASIL and CAA vessels are compared. Both CADASIL and CAA feature abnormal protein accumulation. In CADASIL, the major protein involved is NOTCH3 ectodomain (brown deposits), whereas in CAA, the major protein involved is amyloid-β (Aβ; green deposits). CADASIL vessels also demonstrate dramatic intimal hyperplasia with accumulation of intimal proteins. Both CADASIL and CAA vessels involve significant smooth muscle cell degeneration in the medial layer and hyalinization of the vessel walls. B: Examination of published literature indicated 378 proteins differentially regulated in CADASIL and 58 proteins differentially regulated in vascular CAA. Of these, approximately 33% of the proteins differentially regulated in vascular CAA overlap with those differentially regulated in CADASIL. C: STRING version 11 analysis shows a high degree of interconnectedness among the shared proteins.⁸² Only norrin (NDP) does not have any known or predicted interactions with the other proteins. APCS, serum amyloid protein; APOE, apolipoprotein E; CLU, clusterin; COL1A2, collagen α-2(I) chain; COL6A2, collagen α-2(VI) chain; COL6A3, collagen α-3(VI) chain; C4A, complement C4-A; CST3, cystatin C; FN1, fibronectin; GFAP, glial fibrillary acidic protein; HSPG2, basement membrane–specific heparan sulfate proteoglycan core protein; HTRA1, serine protease HTRA1; LAMC1, laminin subunit γ 1; NFASC, neurofascin; PTGDS, prostaglandin H2 D isomerase; TIMP3, metalloproteinase inhibitor 3; TPM1, tropomyosin α 1 chain; VTN, vitronectin.