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dc.contributor.authorArnold, Matthias
dc.contributor.authorNho, Kwangsik
dc.contributor.authorKueider-Paisley, Alexandra
dc.contributor.authorMassaro, Tyler
dc.contributor.authorHuynh, Kevin
dc.contributor.authorBrauner, Barbara
dc.contributor.authorMahmoudianDehkordi, Siamak
dc.contributor.authorLouie, Gregory
dc.contributor.authorMoseley, M Arthur
dc.contributor.authorThompson, J Will
dc.contributor.authorJohn-Williams, Lisa St
dc.contributor.authorTenenbaum, Jessica D
dc.contributor.authorBlach, Colette
dc.contributor.authorChang, Rui
dc.contributor.authorBrinton, Roberta D
dc.contributor.authorBaillie, Rebecca
dc.contributor.authorHan, Xianlin
dc.contributor.authorTrojanowski, John Q
dc.contributor.authorShaw, Leslie M
dc.contributor.authorMartins, Ralph
dc.contributor.authorWeiner, Michael W
dc.contributor.authorTrushina, Eugenia
dc.contributor.authorToledo, Jon B
dc.contributor.authorMeikle, Peter J
dc.contributor.authorBennett, David A
dc.contributor.authorKrumsiek, Jan
dc.contributor.authorDoraiswamy, P Murali
dc.contributor.authorSaykin, Andrew J
dc.contributor.authorKaddurah-Daouk, Rima
dc.contributor.authorKastenmüller, Gabi
dc.date.accessioned2020-09-05T01:15:43Z
dc.date.available2020-09-05T01:15:43Z
dc.date.issued2020-03-02
dc.identifier.citationArnold, M., Nho, K., Kueider-Paisley, A. et al. Sex and APOE ε4 genotype modify the Alzheimer’s disease serum metabolome. Nat Commun 11, 1148 (2020). https://doi.org/10.1038/s41467-020-14959-wen_US
dc.identifier.issn2041-1723
dc.identifier.pmid32123170
dc.identifier.doi10.1038/s41467-020-14959-w
dc.identifier.urihttp://hdl.handle.net/10150/642589
dc.description.abstractSex and the APOE epsilon 4 genotype are important risk factors for late-onset Alzheimer's disease. In the current study, the authors investigate how sex and APOE epsilon 4 genotype modify the association between Alzheimer's disease biomarkers and metabolites in serum. Late-onset Alzheimer's disease (AD) can, in part, be considered a metabolic disease. Besides age, female sex and APOE epsilon 4 genotype represent strong risk factors for AD that also give rise to large metabolic differences. We systematically investigated group-specific metabolic alterations by conducting stratified association analyses of 139 serum metabolites in 1,517 individuals from the AD Neuroimaging Initiative with AD biomarkers. We observed substantial sex differences in effects of 15 metabolites with partially overlapping differences for APOE epsilon 4 status groups. Several group-specific metabolic alterations were not observed in unstratified analyses using sex and APOE epsilon 4 as covariates. Combined stratification revealed further subgroup-specific metabolic effects limited to APOE epsilon 4+ females. The observed metabolic alterations suggest that females experience greater impairment of mitochondrial energy production than males. Dissecting metabolic heterogeneity in AD pathogenesis can therefore enable grading the biomedical relevance for specific pathways within specific subgroups, guiding the way to personalized medicine.en_US
dc.language.isoenen_US
dc.publisherNATURE PUBLISHING GROUPen_US
dc.rightsCopyright © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by/4.0/.en_US
dc.titleSex and APOE ε4 genotype modify the Alzheimer's disease serum metabolomeen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Ctr Innovat Brain Scien_US
dc.contributor.departmentUniv Arizona, Coll Med, Dept Pharmacolen_US
dc.contributor.departmentUniv Arizona, Coll Med, Dept Neurolen_US
dc.identifier.journalNATURE COMMUNICATIONSen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleNature communications
dc.source.volume11
dc.source.issue1
dc.source.beginpage1148
dc.source.endpage
refterms.dateFOA2020-09-05T01:15:44Z
dc.source.countryUnited States
dc.source.countryEngland


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