Sex and APOE ε4 genotype modify the Alzheimer's disease serum metabolome
Moseley, M Arthur
Thompson, J Will
John-Williams, Lisa St
Tenenbaum, Jessica D
Brinton, Roberta D
Trojanowski, John Q
Shaw, Leslie M
Weiner, Michael W
Toledo, Jon B
Meikle, Peter J
Bennett, David A
Doraiswamy, P Murali
Saykin, Andrew J
AffiliationUniv Arizona, Ctr Innovat Brain Sci
Univ Arizona, Coll Med, Dept Pharmacol
Univ Arizona, Coll Med, Dept Neurol
MetadataShow full item record
PublisherNATURE PUBLISHING GROUP
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-w
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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.
NoteOpen access journal
VersionFinal published version
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