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Sex and APOE ε4 genotype modify the Alzheimer's disease serum metabolome.
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.
Afiliação
  • Arnold M; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
  • Nho K; Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  • Kueider-Paisley A; Department of Radiology and Imaging Sciences and the Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Massaro T; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
  • Huynh K; Duke Clinical Research Institute, Duke University, Durham, NC, USA.
  • Brauner B; Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
  • MahmoudianDehkordi S; Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  • Louie G; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
  • Moseley MA; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
  • Thompson JW; Duke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
  • John-Williams LS; Duke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
  • Tenenbaum JD; Duke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.
  • Blach C; Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
  • Chang R; Duke Molecular Physiology Institute, Duke University, Durham, NC, USA.
  • Brinton RD; Center for Innovation in Brain Science, University of Arizona, Tucson, AZ, USA.
  • Baillie R; Center for Innovation in Brain Science, University of Arizona, Tucson, AZ, USA.
  • Han X; Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA.
  • Trojanowski JQ; Department of Neurology, College of Medicine, University of Arizona, Tucson, AZ, USA.
  • Shaw LM; Rosa & Co LLC, San Carlos, CA, USA.
  • Martins R; University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
  • Weiner MW; Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Trushina E; Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Toledo JB; School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
  • Meikle PJ; Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.
  • Bennett DA; Center for Imaging of Neurodegenerative Diseases, Department of Radiology, San Francisco VA Medical Center/University of California San Francisco, San Francisco, CA, USA.
  • Krumsiek J; Department of Neurology, Mayo Clinic, Rochester, MN, USA.
  • Doraiswamy PM; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
  • Saykin AJ; Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Kaddurah-Daouk R; Department of Neurology, Houston Methodist Hospital, Houston, TX, USA.
  • Kastenmüller G; Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Nat Commun ; 11(1): 1148, 2020 03 02.
Article em En | MEDLINE | ID: mdl-32123170
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Apolipoproteínas E / Sangue / Metaboloma / Doença de Alzheimer Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Aged / Female / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Apolipoproteínas E / Sangue / Metaboloma / Doença de Alzheimer Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Aged / Female / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article