{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:03:53Z","timestamp":1790712233008,"version":"4.1.0"},"reference-count":44,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2019,9,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Pathogenic variants in the autosomal dominant genes PSEN1, PSEN2, or APP, APOE4 alleles, and rare variants within TREM2, SORL1, and ABCA7 contribute to early-onset Alzheimer\u2019s disease (EOAD). However, sporadic EOAD patients have been insufficiently studied to define the probability of being a carrier of one of these variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To describe the proportion of each genetic variation among patients with very young-onset sporadic AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We first screened PSEN1, PSEN2, and APP in 154 EOAD patients with an onset before 51 years and a negative family history. Among 99 patients with no mutation (NMC), whole exome sequencing (WES) was performed. We analyzed the APOE genotype and rare protein-truncating or missense predicted damaging variants of TREM2, SORL1, and ABCA7. Neurological examination and cerebrospinal fluid (CSF) biomarkers were systematically retrieved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Nineteen (12.3%) mutation carriers (MC) harbored an APP or PSEN1 pathogenic or likely pathogenic variant. Among the NMC, 54\/99 carried at least one genetic risk factor, including 9 APOE4\/E4 homozygous, 37 APOE4 heterozygous, and 14 with a rare variant in another risk factor gene: 3 SORL1, 4 TREM2, and 9 ABCA7. MC presented an earlier disease onset ( p\u200a&lt;\u200a0.0001) and associated neurologic symptoms more frequently ( p\u200a&lt;\u200a0.002). All but one patient had at least 2 CSF biomarkers in abnormal ranges.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The genetic component of very early sporadic EOAD gathers a substantial proportion of pathogenic variants in autosomal dominant genes and an even higher proportion of patients carrying genetic risk factors, suggesting an oligogenic determinism, even at this range of ages.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-190193","type":"journal-article","created":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T11:29:43Z","timestamp":1564486183000},"page":"227-243","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":35,"title":["Causative Mutations and Genetic Risk Factors in Sporadic Early Onset Alzheimer\u2019s Disease Before 51 Years"],"prefix":"10.1177","volume":"71","author":[{"given":"Morgane","family":"Lacour","sequence":"first","affiliation":[{"name":"Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Neurology and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Quenez","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Rovelet-Lecrux","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Salomon","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Neurology and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Rousseau","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Claire","family":"Richard","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and CNR-MAJ, Normandy Center for Genomic and Personalized Medicine, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muriel","family":"Quillard-Muraine","sequence":"additional","affiliation":[{"name":"Normandie Univ, UNIROUEN, Rouen University Hospital, Biochemistry Laboratory, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Pasquier","sequence":"additional","affiliation":[{"name":"Department of Neurology and CNR-MAJ, Lille University Hospital, Lille, France"},{"name":"Univ Lille, Inserm UMR-S 1171, Distalz, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Rollin-Sillaire","sequence":"additional","affiliation":[{"name":"Department of Neurology and CNR-MAJ, Lille University Hospital, Lille, France"},{"name":"Univ Lille, Inserm UMR-S 1171, Distalz, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Martinaud","sequence":"additional","affiliation":[{"name":"Department of Neurology, Caen 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