Therefore, although canonical NOTCH3 mutations causative for CADASIL are highly stereotyped: (1) cluster in epidermal growth factor–like repeat domains, (2) in exons 3 and 4, and (3) consist in the gain or loss of cysteine; nevertheless, our study reports a possible synergetic effect of common and rare variants in NOTCH3 potentially influencing AD susceptibility through an increased risk for small vessel disease or white matter lesions. Here, NOTCH3 is linked to Alzheimer disease.