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

Aged Alzheimer Disease / blood Apolipoproteins E / genetics Biomarkers / blood Blood / metabolism Cohort Studies Female Genotype Humans Male Metabolome / genetics Mitochondria / genetics Positron-Emission Tomography Sex Factors

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
02 03 2020
Historique:
received: 22 05 2019
accepted: 04 02 2020
entrez: 4 3 2020
pubmed: 4 3 2020
medline: 23 5 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-020-14959-w PMID: 32123170 PMC: PMC7052223
pubmed: 32123170
doi: 10.1038/s41467-020-14959-w
pii: 10.1038/s41467-020-14959-w
pmc: PMC7052223
doi:

Substances chimiques

Apolipoproteins E 0
Biomarkers 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

1148

Subventions

Organisme : NIA NIH HHS
ID : R03 AG054936
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG061356
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG017917
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG059093
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG057452
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG057457
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG026572
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG046171
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046152
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG055549
Pays : United States
Organisme : NLM NIH HHS
ID : R01 LM012535
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG061359
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG061872
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG058942
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG051550
Pays : United States

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Auteurs

Matthias Arnold (M)

Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
ORCID: 0000-0002-4666-0923

Kwangsik Nho (K)

Department of Radiology and Imaging Sciences and the Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.

Alexandra Kueider-Paisley (A)

Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.

Tyler Massaro (T)

Duke Clinical Research Institute, Duke University, Durham, NC, USA.

Kevin Huynh (K)

Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Barbara Brauner (B)

Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

Siamak MahmoudianDehkordi (S)

Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.

Gregory Louie (G)

Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
ORCID: 0000-0002-3267-7070

M Arthur Moseley (MA)

Duke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.

J Will Thompson (JW)

Duke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.

Lisa St John-Williams (LS)

Duke Proteomics and Metabolomics Shared Resource, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.

Jessica D Tenenbaum (JD)

Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
ORCID: 0000-0003-3532-565X

Colette Blach (C)

Duke Molecular Physiology Institute, Duke University, Durham, NC, USA.

Rui Chang (R)

Center for Innovation in Brain Science, University of Arizona, Tucson, AZ, USA.

Roberta D Brinton (RD)

Center for Innovation in Brain Science, University of Arizona, Tucson, AZ, USA.
Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, USA.
Department of Neurology, College of Medicine, University of Arizona, Tucson, AZ, USA.

Rebecca Baillie (R)

Rosa & Co LLC, San Carlos, CA, USA.
ORCID: 0000-0003-3966-6320

Xianlin Han (X)

University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
ORCID: 0000-0002-8615-2413

John Q Trojanowski (JQ)

Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
ORCID: 0000-0002-9239-8794

Leslie M Shaw (LM)

Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Ralph Martins (R)

School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
Department of Biomedical Sciences, Macquarie University, North Ryde, NSW, Australia.

Michael W Weiner (MW)

Center for Imaging of Neurodegenerative Diseases, Department of Radiology, San Francisco VA Medical Center/University of California San Francisco, San Francisco, CA, USA.

Eugenia Trushina (E)

Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.

Jon B Toledo (JB)

Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Neurology, Houston Methodist Hospital, Houston, TX, USA.

Peter J Meikle (PJ)

Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
ORCID: 0000-0002-2593-4665

David A Bennett (DA)

Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.

Jan Krumsiek (J)

Institute for Computational Biomedicine, Englander Institute for Precision Medicine, Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.

P Murali Doraiswamy (PM)

Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
Duke Institute of Brain Sciences, Duke University, Durham, NC, USA.
Department of Medicine, Duke University, Durham, NC, USA.

Andrew J Saykin (AJ)

Department of Radiology and Imaging Sciences and the Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
ORCID: 0000-0002-1376-8532

Rima Kaddurah-Daouk (R)

Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA. kaddu001@mc.duke.edu.
Duke Institute of Brain Sciences, Duke University, Durham, NC, USA. kaddu001@mc.duke.edu.
Department of Medicine, Duke University, Durham, NC, USA. kaddu001@mc.duke.edu.
ORCID: 0000-0003-1858-5732

Gabi Kastenmüller (G)

Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. g.kastenmueller@helmholtz-muenchen.de.
German Center for Diabetes Research (DZD), Neuherberg, Germany. g.kastenmueller@helmholtz-muenchen.de.
ORCID: 0000-0002-2368-7322

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Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
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Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sex and APOE ε4 genotype modify the...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Sex and APOE ε4 genotype modify the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Lipoprotéines › Apolipoprotéines › Apolipoprotéines E › Sex and APOE ε4 genotype modify the...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Sex and APOE ε4 genotype modify the...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Sang › Sex and APOE ε4 genotype modify the...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Sex and APOE ε4 genotype modify the...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Sex and APOE ε4 genotype modify the...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Sex and APOE ε4 genotype modify the...
questionsmedicales.fr › Métabolisme › Métabolome › Sex and APOE ε4 genotype modify the...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Mitochondries › Sex and APOE ε4 genotype modify the...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Techniques de diagnostic radioisotopique › Scintigraphie › Tomoscintigraphie › Tomographie par émission de positons › Sex and APOE ε4 genotype modify the...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Facteurs épidémiologiques › Facteurs sexuels › Sex and APOE ε4 genotype modify the...