Sex and APOE ε4 genotype modify the Alzheimer's disease serum metabolome
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Author
Arnold, MatthiasNho, 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
Affiliation
Univ Arizona, Ctr Innovat Brain SciUniv Arizona, Coll Med, Dept Pharmacol
Univ Arizona, Coll Med, Dept Neurol
Issue Date
2020-03-02
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NATURE PUBLISHING GROUPCitation
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-wJournal
NATURE COMMUNICATIONSRights
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 journalISSN
2041-1723PubMed ID
32123170Version
Final published versionae974a485f413a2113503eed53cd6c53
10.1038/s41467-020-14959-w
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