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Pandey, R.S.* ; Arnold, M. ; Batra, R.* ; Krumsiek, J.* ; Kotredes, K.P.* ; Garceau, D.* ; Williams, H.* ; Sasner, M.* ; Howell, G.R.* ; Kaddurah-Daouk, R.* ; Carter, G.W.*

Metabolomics profiling reveals distinct, sex-specific signatures in serum and brain metabolomes in mouse models of Alzheimer's disease.

Alzheimers Dement., DOI: 10.1002/alz.13851 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
INTRODUCTION: Increasing evidence suggests that metabolic impairments contribute to early Alzheimer's disease (AD) mechanisms and subsequent dementia. Signals in metabolic pathways conserved across species can facilitate translation. METHODS: We investigated differences in serum and brain metabolites between the early-onset 5XFAD and late-onset LOAD1 (APOE4.Trem2*R47H) mouse models of AD to C57BL/6J controls at 6 months of age. RESULTS: We identified sex differences for several classes of metabolites, such as glycerophospholipids, sphingolipids, and amino acids. Metabolic signatures were notably different between brain and serum in both mouse models. The 5XFAD mice exhibited stronger differences in brain metabolites, whereas LOAD1 mice showed more pronounced differences in serum. DISCUSSION: Several of our findings were consistent with results in humans, showing glycerophospholipids reduction in serum of apolipoprotein E (apoE) ε4 carriers and replicating the serum metabolic imprint of the APOE ε4 genotype. Our work thus represents a significant step toward translating metabolic dysregulation from model organisms to human AD. HIGHLIGHTS: This was a metabolomic assessment of two mouse models relevant to Alzheimer's disease. Mouse models exhibit broad sex-specific metabolic differences, similar to human study cohorts. The early-onset 5XFAD mouse model primarily alters brain metabolites while the late-onset LOAD1 model primarily changes serum metabolites. Apolipoprotein E (apoE) ε4 mice recapitulate glycerophospolipid signatures of human APOE ε4 carriers in both brain and serum.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 5xfad ; Alzheimer's Disease ; Animal Models ; Apolipoprotein E ; Metabolomics; Amyloid-beta; Oxidative Stress; Risk-factors; Genetics; Neurodegeneration; Cholesterol; Involvement; Dysfunction; Pathways; Dementia
ISSN (print) / ISBN 1552-5260
e-ISSN 1552-5279
Journal Alzheimer's & Dementia
Publisher Elsevier
Publishing Place New York, NY [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants National Institute on Aging
NIA
ADNI - Alzheimer's Disease Neuroimaging Initiative (ADNI
Alzheimer's Disease Metabolomics Consortium
FNIH
Duke Metabolomics and Proteomics Shared Resource, a member of the ADMC
National Institute on Aging of the National Institutes of Health
National Institutes of Health)
DOD ADNI (Department of Defense)
National Institute of Biomedical Imaging and Bioengineering
Meso Scale Diagnostics, LLC
Novartis Pharmaceuticals Corporation
Pfizer Inc.
Piramal Imaging
Takeda Pharmaceutical Company
Canadian Institutes of Health Research
ADNI clinical sites in Canada
Foundation for the National Institutes of Health
Northern California Institute for Research and Education
Laboratory for Neuro Imaging at the University of Southern California
Illinois Department of Public Health (ROSMAP)
Merck Co., Inc.
Lumosity
Johnson & Johnson Pharmaceutical Research & Development LLC
Alzheimer's Association
Alzheimer's Drug Discovery Foundation
Araclon Biotech
Biogen
CereSpir, Inc.
Cogstate
Elan Pharmaceuticals, Inc.
Eli Lilly and Company
EuroImmun
Fujirebio
Janssen Alzheimer Immunotherapy Research & Development, LLC
Translational Genomics Research Institute