We find that NOTCH3 ECD depositions around capillaries as well as NOTCH3 ECD levels in the blood are reduced in CADASIL mice treated with the NOTCH3 EGF1–5‐directed vaccine for 4 months and that the vaccine does not appear to interfere with the role of Notch signaling for vascular integrity or induce inflammation, neurodegeneration or kidney damage. The gene discussed is NOTCH3; the disease is Nephropathy.