TY - JOUR
T1 - Sex and APOE ε4 genotype modify the Alzheimer’s disease serum metabolome
AU - Arnold, Matthias
AU - Nho, Kwangsik
AU - Kueider-Paisley, Alexandra
AU - Massaro, Tyler
AU - Huynh, Kevin
AU - Brauner, Barbara
AU - MahmoudianDehkordi, Siamak
AU - Louie, Gregory
AU - Moseley, M. Arthur
AU - Thompson, J. Will
AU - John-Williams, Lisa St
AU - Tenenbaum, Jessica D.
AU - Blach, Colette
AU - Chang, Rui
AU - Brinton, Roberta D.
AU - Baillie, Rebecca
AU - Han, Xianlin
AU - Trojanowski, John Q.
AU - Shaw, Leslie M.
AU - Martins, Ralph
AU - Weiner, Michael W.
AU - Trushina, Eugenia
AU - Toledo, Jon B.
AU - Meikle, Peter J.
AU - Bennett, David A.
AU - Krumsiek, Jan
AU - Doraiswamy, P. Murali
AU - Saykin, Andrew J.
AU - Kaddurah-Daouk, Rima
AU - Kastenmüller, Gabi
N1 - Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2020/3/2
Y1 - 2020/3/2
N2 - Late-onset Alzheimer’s disease (AD) can, in part, be considered a metabolic disease. Besides age, female sex and APOE ε4 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 ε4 status groups. Several group-specific metabolic alterations were not observed in unstratified analyses using sex and APOE ε4 as covariates. Combined stratification revealed further subgroup-specific metabolic effects limited to APOE ε4+ 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.
AB - Late-onset Alzheimer’s disease (AD) can, in part, be considered a metabolic disease. Besides age, female sex and APOE ε4 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 ε4 status groups. Several group-specific metabolic alterations were not observed in unstratified analyses using sex and APOE ε4 as covariates. Combined stratification revealed further subgroup-specific metabolic effects limited to APOE ε4+ 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.
UR - http://www.scopus.com/inward/record.url?scp=85080889707&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-14959-w
DO - 10.1038/s41467-020-14959-w
M3 - Article
C2 - 32123170
AN - SCOPUS:85080889707
SN - 2041-1723
VL - 11
SP - 1
EP - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1148
ER -