FIGURE 1.

NOTCH3 score and GOM load are significantly lower in CADASIL patients with NOTCH3 ^cys variants in EGFr 7–34 in skin biopsies. (A,B) representative images of NOTCH3 immunostaining on skin vessels of (A) controls and (B) CADASIL patients. Controls show a negative NOTCH3 staining, whilst CADASIL patients show a positive and granular NOTCH3 staining. (C) NOTCH3 score: The vessel wall area positive for granular NOTCH3^ECD staining is expressed as the percentage of the total vessel wall area. (D) Patients with NOTCH3 ^cys variants located in EGFr 7–34 have lower NOTCH3 scores than patients with EGFr 1–6 variants (median NOTCH3 score 5.2% [IQR 11.1] versus 48.6% [48.2], P = 1.3·10⁻⁵). (E,F) patients with NOTCH3 ^cys variants located in EGFr 7–34 have less GOM‐positive vessels than patients with EGFr 1–6 variants (median 0.0% [IQR 5.6] versus 18.8% [10.9], P = 6.4·10⁻⁵) and a lower overall GOM count (median 0.0 GOM/1000 μm [IQR 1.6] versus 9.8 [15.2], P = 8.2·10⁻⁵). (G) GOM deposits are more prevalent in arterioles than in capillaries and venules (median 11.2 GOM/1000 μm [IQR 50.6], 0.0 [3.3] and 0.0 [0.7], respectively). (H) The difference in GOM count between the EGFr groups was also observed in arterioles, capillaries and venules separately. To facilitate interpretation, data is plotted on log₁₀‐axis and represent mean ± standard deviation in H. In D‐G, data represent median ± interquartile range. P values are calculated from transformed variables