{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:44:40Z","timestamp":1788385480933,"version":"build-2803163510"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T00:00:00Z","timestamp":1732320000000},"content-version":"vor","delay-in-days":53,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp;amp; Dem Diag Ass &amp;amp; Dis Mo"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Genetics of cerebral amyloid angiopathy (CAA) remains understudied.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We assessed variants in Alzheimer's disease (AD) risk factor genes and differential diagnosis genes by performing exome sequencing among 78 patients with early\u2010onset definite or probable CAA, after negative screening for APP mutation or duplication.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Among 14 genes involved in non\u2010A\u03b2 CAA, or vascular leukoencephalopathies, we detected pathogenic NOTCH3 variants in two patients, who exhibited lobar hematomas at the ages of 58 and 65, leading to a diagnosis redirection toward CADASIL. Of the remaining 76 patients, 23.1% carried at least one apolipoprotein E (APOE) \u03b52 allele and 43.6% carried at least one APOE \u03b54 allele, known as\u00a0CAA risk factors. A total of 15 out of 76 (19.7%) carried either a loss\u2010of\u2010function or a rare predicted damaging missense or known AD risk variant in SORL1,\u00a0TREM2,\u00a0ABCA7,\u00a0ABCA1,\u00a0and\u00a0ATP8B4.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Exome sequencing allowed the redirection toward CADASIL in two patients and suggested shared genetic factors between AD and CAA, beyond the APOE gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The genetic component of cerebral amyloid angiopathy (CAA) remains understudied.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Rare differential diagnoses such as CADASIL should be considered, even in cases of cerebral hemorrhage.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our study suggests shared genetic factors between AD and CAA, beyond the <jats:italic>APOE<\/jats:italic> gene.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Rare variants in <jats:italic>SORL1, TREM2<\/jats:italic>, <jats:italic>ABCA7, ABCA1<\/jats:italic> and <jats:italic>ATP8B4<\/jats:italic> might be susceptibility factors in early\u2010onset CAA.,<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/dad2.70027","type":"journal-article","created":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T09:08:47Z","timestamp":1732352927000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Input of exome sequencing in early\u2010onset cerebral amyloid angiopathy"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8458-7683","authenticated-orcid":false,"given":"Lou","family":"Grangeon","sequence":"first","affiliation":[{"name":"Department of Neurology and CNRMAJ Univ Rouen Normandie  Rouen 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