Input of exome sequencing in early‐onset cerebral amyloid angiopathy
Abstract INTRODUCTION Genetics of cerebral amyloid angiopathy (CAA) remains understudied. METHODS We assessed variants in Alzheimer's disease (AD) risk factor genes and differential diagnosis genes by performing exome sequencing among 78 patients with early‐onset definite or probable CAA, after...
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Wiley
2024-10-01
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| Series: | Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring |
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| Online Access: | https://doi.org/10.1002/dad2.70027 |
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| author | Lou Grangeon Camille Charbonnier Stéphane Rousseau Anne Claire Richard Olivier Quenez Aline Zarea Anne Boland Robert Olaso Jean‐François Deleuze CAA study group Elisabeth Tournier‐Lasserve Gael Nicolas David Wallon |
| author_facet | Lou Grangeon Camille Charbonnier Stéphane Rousseau Anne Claire Richard Olivier Quenez Aline Zarea Anne Boland Robert Olaso Jean‐François Deleuze CAA study group Elisabeth Tournier‐Lasserve Gael Nicolas David Wallon |
| author_sort | Lou Grangeon |
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| description | Abstract INTRODUCTION Genetics of cerebral amyloid angiopathy (CAA) remains understudied. METHODS We assessed variants in Alzheimer's disease (AD) risk factor genes and differential diagnosis genes by performing exome sequencing among 78 patients with early‐onset definite or probable CAA, after negative screening for APP mutation or duplication. RESULTS Among 14 genes involved in non‐Aβ 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) ε2 allele and 43.6% carried at least one APOE ε4 allele, known as CAA risk factors. A total of 15 out of 76 (19.7%) carried either a loss‐of‐function or a rare predicted damaging missense or known AD risk variant in SORL1, TREM2, ABCA7, ABCA1, and ATP8B4. DISCUSSION Exome sequencing allowed the redirection toward CADASIL in two patients and suggested shared genetic factors between AD and CAA, beyond the APOE gene. Highlights The genetic component of cerebral amyloid angiopathy (CAA) remains understudied. Rare differential diagnoses such as CADASIL should be considered, even in cases of cerebral hemorrhage. Our study suggests shared genetic factors between AD and CAA, beyond the APOE gene. Rare variants in SORL1, TREM2, ABCA7, ABCA1 and ATP8B4 might be susceptibility factors in early‐onset CAA., |
| format | Article |
| id | doaj-art-06b0b44dc4d549e1a36520b49a07fea5 |
| institution | OA Journals |
| issn | 2352-8729 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring |
| spelling | doaj-art-06b0b44dc4d549e1a36520b49a07fea52025-08-20T02:00:55ZengWileyAlzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring2352-87292024-10-01164n/an/a10.1002/dad2.70027Input of exome sequencing in early‐onset cerebral amyloid angiopathyLou Grangeon0Camille Charbonnier1Stéphane Rousseau2Anne Claire Richard3Olivier Quenez4Aline Zarea5Anne Boland6Robert Olaso7Jean‐François Deleuze8CAA study groupElisabeth Tournier‐Lasserve9Gael Nicolas10David Wallon11Department of Neurology and CNRMAJ Univ Rouen Normandie Rouen FranceDepartment of Genetics Department of Biostatistics and CNRMAJ Univ Rouen Normandie Rouen FranceDepartment of Genetics and CNRMAJ Univ Rouen Normandie Rouen FranceDepartment of Genetics and CNRMAJ Univ Rouen Normandie Rouen FranceDepartment of Genetics and CNRMAJ Univ Rouen Normandie Rouen FranceDepartment of Neurology and CNRMAJ Univ Rouen Normandie Rouen FranceUniversité Paris‐Saclay CEA Centre National de Recherche en Génomique Humaine (CNRGH) Evry FranceUniversité Paris‐Saclay CEA Centre National de Recherche en Génomique Humaine (CNRGH) Evry FranceUniversité Paris‐Saclay CEA Centre National de Recherche en Génomique Humaine (CNRGH) Evry FranceUniversité Paris‐Cité Assistance‐Publique Hôpitaux de Paris INSERM Paris FranceDepartment of Genetics and CNRMAJ Univ Rouen Normandie Rouen FranceDepartment of Neurology and CNRMAJ Univ Rouen Normandie Rouen FranceAbstract INTRODUCTION Genetics of cerebral amyloid angiopathy (CAA) remains understudied. METHODS We assessed variants in Alzheimer's disease (AD) risk factor genes and differential diagnosis genes by performing exome sequencing among 78 patients with early‐onset definite or probable CAA, after negative screening for APP mutation or duplication. RESULTS Among 14 genes involved in non‐Aβ 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) ε2 allele and 43.6% carried at least one APOE ε4 allele, known as CAA risk factors. A total of 15 out of 76 (19.7%) carried either a loss‐of‐function or a rare predicted damaging missense or known AD risk variant in SORL1, TREM2, ABCA7, ABCA1, and ATP8B4. DISCUSSION Exome sequencing allowed the redirection toward CADASIL in two patients and suggested shared genetic factors between AD and CAA, beyond the APOE gene. Highlights The genetic component of cerebral amyloid angiopathy (CAA) remains understudied. Rare differential diagnoses such as CADASIL should be considered, even in cases of cerebral hemorrhage. Our study suggests shared genetic factors between AD and CAA, beyond the APOE gene. Rare variants in SORL1, TREM2, ABCA7, ABCA1 and ATP8B4 might be susceptibility factors in early‐onset CAA.,https://doi.org/10.1002/dad2.70027Alzheimer diseaseCADASILcerebral angiopathy amyloidgenetic risk factorsintracerebral hemorrhage |
| spellingShingle | Lou Grangeon Camille Charbonnier Stéphane Rousseau Anne Claire Richard Olivier Quenez Aline Zarea Anne Boland Robert Olaso Jean‐François Deleuze CAA study group Elisabeth Tournier‐Lasserve Gael Nicolas David Wallon Input of exome sequencing in early‐onset cerebral amyloid angiopathy Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring Alzheimer disease CADASIL cerebral angiopathy amyloid genetic risk factors intracerebral hemorrhage |
| title | Input of exome sequencing in early‐onset cerebral amyloid angiopathy |
| title_full | Input of exome sequencing in early‐onset cerebral amyloid angiopathy |
| title_fullStr | Input of exome sequencing in early‐onset cerebral amyloid angiopathy |
| title_full_unstemmed | Input of exome sequencing in early‐onset cerebral amyloid angiopathy |
| title_short | Input of exome sequencing in early‐onset cerebral amyloid angiopathy |
| title_sort | input of exome sequencing in early onset cerebral amyloid angiopathy |
| topic | Alzheimer disease CADASIL cerebral angiopathy amyloid genetic risk factors intracerebral hemorrhage |
| url | https://doi.org/10.1002/dad2.70027 |
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