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Causative Mutations and Genetic Risk Factors in Sporadic Early Onset Alzheimer's Disease Before 51 Years

dc.rights.licenseopenen_US
dc.contributor.authorLACOUR, M.
dc.contributor.authorQUENEZ, O.
dc.contributor.authorROVELET-LECRUX, A.
dc.contributor.authorSALOMON, B.
dc.contributor.authorROUSSEAU, S.
dc.contributor.authorRICHARD, A. C.
dc.contributor.authorQUILLARD-MURAINE, M.
dc.contributor.authorPASQUIER, F.
dc.contributor.authorROLLIN-SILLAIRE, A.
dc.contributor.authorMARTINAUD, O.
dc.contributor.authorZAREA, A.
dc.contributor.authorDE LA SAYETTE, V.
dc.contributor.authorBOUTOLEAU-BRETONNIERE, C.
dc.contributor.authorETCHARRY-BOUYX, F.
dc.contributor.authorCHAUVIRE, V.
dc.contributor.authorSARAZIN, M.
dc.contributor.authorLE BER, I.
dc.contributor.authorEPELBAUM, S.
dc.contributor.authorJONVEAUX, T.
dc.contributor.authorROUAUD, O.
dc.contributor.authorCECCALDI, M.
dc.contributor.authorGODEFROY, O.
dc.contributor.authorFORMAGLIO, M.
dc.contributor.authorCROISILE, B.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorAURIACOMBE, Sophie
dc.contributor.authorMAGNIN, E.
dc.contributor.authorSAUVEE, M.
dc.contributor.authorMARELLI, C.
dc.contributor.authorGABELLE, A.
dc.contributor.authorPARIENTE, J.
dc.contributor.authorPAQUET, C.
dc.contributor.authorBOLAND, A.
dc.contributor.authorDELEUZE, J. F.
dc.contributor.authorCAMPION, D.
dc.contributor.authorHANNEQUIN, D.
dc.contributor.authorNICOLAS, G.
dc.contributor.authorWALLON, D.
dc.date.accessioned2020-06-25T08:00:05Z
dc.date.available2020-06-25T08:00:05Z
dc.date.issued2019-08
dc.identifier.issn1875-8908 (Electronic) 1387-2877 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/8183
dc.description.abstractEnBACKGROUND: 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's disease (EOAD). However, sporadic EOAD patients have been insufficiently studied to define the probability of being a carrier of one of these variants. OBJECTIVE: To describe the proportion of each genetic variation among patients with very young-onset sporadic AD. METHODS: 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. RESULTS: 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 < 0.0001) and associated neurologic symptoms more frequently (p < 0.002). All but one patient had at least 2 CSF biomarkers in abnormal ranges. CONCLUSION: 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.
dc.language.isoENen_US
dc.subject.enSEPIA
dc.title.enCausative Mutations and Genetic Risk Factors in Sporadic Early Onset Alzheimer's Disease Before 51 Years
dc.title.alternativeJ Alzheimers Disen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.3233/jad-190193en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed31381512en_US
bordeaux.journalJournal of Alzheimer's diseaseen_US
bordeaux.page227-243en_US
bordeaux.volume71en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=Journal%20of%20Alzheimer's%20disease&amp;rft.date=2019-08&amp;rft.volume=71&amp;rft.issue=1&amp;rft.spage=227-243&amp;rft.epage=227-243&amp;rft.eissn=1875-8908%20(Electronic)%201387-2877%20(Linking)&amp;rft.issn=1875-8908%20(Electronic)%201387-2877%20(Linking)&amp;rft.au=LACOUR,%20M.&amp;QUENEZ,%20O.&amp;ROVELET-LECRUX,%20A.&amp;SALOMON,%20B.&amp;ROUSSEAU,%20S.&amp;rft.genre=article


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