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Besides, there may be a pathogenic link between <jats:italic>NOTCH3<\/jats:italic> variants and Alzheimer's disease (AD). We aimed to study the role of <jats:italic>NOTCH3<\/jats:italic> variants in AD and SVaD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited 763 patients with dementia (667 AD and 96 SVaD) and 365 healthy controls from the Southern Han Chinese population. Targeted capture sequencing was performed on <jats:italic>NOTCH3<\/jats:italic> coding and adjacent intron regions to detect the pathogenic variants in AD and SVaD. The relationship between common or rare <jats:italic>NOTCH3<\/jats:italic> variants and AD was further analyzed using Plink1.9.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Five known pathogenic variants (p.R182C, p.C201S, p.R544C, p.R607C, and p.R1006C) and two novel likely pathogenic variants (p.C201F and p.C1061F) were detected in 16 SVaD patients. Additionally, no pathogenic or likely pathogenic variants were found in AD patients. <jats:italic>NOTCH3<\/jats:italic> was not associated with AD in either single\u2010variant association analysis or gene\u2010based association analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings broaden the mutational spectrum of <jats:italic>NOTCH3<\/jats:italic> and validate the pathogenic role of <jats:italic>NOTCH3<\/jats:italic> mutations in SVaD, but do not support the notion that <jats:italic>NOTCH3<\/jats:italic> variation influences the risk of AD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13647","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T12:27:03Z","timestamp":1620131223000},"page":"930-940","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The role of <i>NOTCH3<\/i> variants in Alzheimer's disease and subcortical vascular dementia 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