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Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker-based case-control study

dc.rights.licenseopenen_US
dc.contributor.authorSADDIKI, H.
dc.contributor.authorFAYOSSE, A.
dc.contributor.authorCOGNAT, E.
dc.contributor.authorSABIA, S.
dc.contributor.authorENGELBORGHS, S.
dc.contributor.authorWALLON, D.
dc.contributor.authorALEXOPOULOS, P.
dc.contributor.authorBLENNOW, K.
dc.contributor.authorZETTERBERG, H.
dc.contributor.authorPARNETTI, L.
dc.contributor.authorZERR, I.
dc.contributor.authorHERMANN, P.
dc.contributor.authorGABELLE, A.
dc.contributor.authorBOADA, M.
dc.contributor.authorORELLANA, A.
dc.contributor.authorDE ROJAS, I.
dc.contributor.authorLILAMAND, M.
dc.contributor.authorBJERKE, M.
dc.contributor.authorVAN BROECKHOVEN, C.
dc.contributor.authorFAROTTI, L.
dc.contributor.authorSALVADORI, N.
dc.contributor.authorDIEHL-SCHMID, J.
dc.contributor.authorGRIMMER, T.
dc.contributor.authorHOURREGUE, C.
dc.contributor.authorDUGRAVOT, A.
dc.contributor.authorNICOLAS, G.
dc.contributor.authorLAPLANCHE, J. L.
dc.contributor.authorLEHMANN, S.
dc.contributor.authorBOUAZIZ-AMAR, E.
dc.contributor.authorHUGON, J.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTZOURIO, Christophe
dc.contributor.authorSINGH-MANOUX, A.
dc.contributor.authorPAQUET, C.
dc.contributor.authorDUMURGIER, J.
dc.date.accessioned2021-02-25T15:52:11Z
dc.date.available2021-02-25T15:52:11Z
dc.date.issued2020
dc.identifier.issn1549-1676 (Electronic) 1549-1277 (Linking)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26360
dc.description.abstractEnBackground The ε4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association between APOE genotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of β-amyloid peptide (A, β-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. Methods and findings This case–control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44–96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44–94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least one APOE ε4 allele. Compared with non-ε4 carriers, heterozygous ε4 carriers had a 4.6 (95% confidence interval 4.1–5.2; p < 0.001) and ε4/ε4 homozygotes a 25.4 (20.4–31.2; p < 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (p for interaction < 0.001). The PAF associated with carrying at least one ε4 allele was greatest in the 65–70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect of APOE ε2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. Conclusions In this study, we found that AD diagnosis based on biomarkers was associated with APOE ε4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65–70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE ε4 at the population level.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subjectHEALTHY
dc.title.enAge and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker-based case-control study
dc.title.alternativePlos Meden_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1371/journal.pmed.1003289en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed32817639en_US
bordeaux.journalPLoS Medicineen_US
bordeaux.pagee1003289en_US
bordeaux.volume17en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - U1219en_US
bordeaux.issue8en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.teamHEALTHY_BPH
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03152605
hal.version1
hal.date.transferred2021-02-25T15:52:18Z
hal.exporttrue
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