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    Sex and APOE ε4 genotype modify the Alzheimer's disease serum metabolome

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    Author
    Arnold, Matthias
    Nho, Kwangsik
    Kueider-Paisley, Alexandra
    Massaro, Tyler
    Huynh, Kevin
    Brauner, Barbara
    MahmoudianDehkordi, Siamak
    Louie, Gregory
    Moseley, M Arthur
    Thompson, J Will
    John-Williams, Lisa St
    Tenenbaum, Jessica D
    Blach, Colette
    Chang, Rui
    Brinton, Roberta D
    Baillie, Rebecca
    Han, Xianlin
    Trojanowski, John Q
    Shaw, Leslie M
    Martins, Ralph
    Weiner, Michael W
    Trushina, Eugenia
    Toledo, Jon B
    Meikle, Peter J
    Bennett, David A
    Krumsiek, Jan
    Doraiswamy, P Murali
    Saykin, Andrew J
    Kaddurah-Daouk, Rima
    Kastenmüller, Gabi
    Show allShow less
    Affiliation
    Univ Arizona, Ctr Innovat Brain Sci
    Univ Arizona, Coll Med, Dept Pharmacol
    Univ Arizona, Coll Med, Dept Neurol
    Issue Date
    2020-03-02
    
    Metadata
    Show full item record
    Publisher
    NATURE PUBLISHING GROUP
    Citation
    Arnold, 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-w
    Journal
    NATURE COMMUNICATIONS
    Rights
    Copyright © 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/.
    Collection Information
    This 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.
    Abstract
    Sex 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.
    Note
    Open access journal
    ISSN
    2041-1723
    PubMed ID
    32123170
    DOI
    10.1038/s41467-020-14959-w
    Version
    Final published version
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-020-14959-w
    Scopus Count
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