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Arnold, M. ; Nho, K.* ; Kueider-Paisley, A.* ; Massaro, T.* ; Huynh, K.* ; Brauner, B. ; MahmoudianDehkordi, S.* ; Louie, G.* ; Moseley, M.A.* ; Thompson, J.W.* ; St John-Williams, L.* ; Tenenbaum, J.D.* ; Blach, C.* ; Chang, R.* ; Brinton, R.D.* ; Baillie, R.* ; Han, X.* ; Trojanowski, J.Q.* ; Shaw, L.M.* ; Martins, R.* ; Weiner, M.W.* ; Trushina, E.* ; Toledo, J.B.* ; Meikle, P.J.* ; Bennett, D.A.* ; Krumsiek, J.* ; Doraiswamy, P.M.* ; Saykin, A.J.* ; Kaddurah-Daouk, R.* ; Kastenmüller, G.

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

Nat. Commun. 11:1148 (2020)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Apolipoprotein-e Genotype; Chain Amino-acids; Cognitive Impairment; Insulin-resistance; Brain Structure; Risk; Association; Gender; Dementia; Age
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 11, Issue: 1, Pages: , Article Number: 1148 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Bioinformatics and Systems Biology (IBIS)