A previous study reported an association of AD with a distinct NOTCH3 mutation (p.R1231C) in a Turkish family46; however, this variant was detected in only 1 affected member and there is conflicting information about its pathogenicity.47 Sassi et al48 tested the hypothesis that genes associated with mendelian adult-onset leukodystrophy are also associated with AD in a sample including 332 sporadic participants with AD and 676 controls and found a significant gene-based association with NOTCH3, a result driven primarily by a common synonymous coding variant. This evidence concerns the gene NOTCH3 and Alzheimer disease.