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Arnold, M. ; Buyukozkan, M.* ; Doraiswamy, P.M.* ; Nho, K.* ; Wu, T. ; Gudnason, V.* ; Launer, L.J.* ; Wang-Sattler, R. ; Adamski, J. ; de Jager, P.L.* ; Ertekin-Taner, N.* ; Bennett, D.A.* ; Saykin, A.J.* ; Peters, A. ; Suhre, K.* ; Kaddurah-Daouk, R.* ; Kastenmüller, G. ; Krumsiek, J.*

Individual bioenergetic capacity as a potential source of resilience to Alzheimer's disease.

Nat. Commun. 16:1910 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Impaired glucose uptake in the brain is an early presymptomatic manifestation of Alzheimer's disease (AD), with symptom-free periods of varying duration that likely reflect individual differences in metabolic resilience. We propose a systemic "bioenergetic capacity", the individual ability to maintain energy homeostasis under pathological conditions. Using fasting serum acylcarnitine profiles from the AD Neuroimaging Initiative as a blood-based readout for this capacity, we identified subgroups with distinct clinical and biomarker presentations of AD. Our data suggests that improving beta-oxidation efficiency can decelerate bioenergetic aging and disease progression. The estimated treatment effects of targeting the bioenergetic capacity were comparable to those of recently approved anti-amyloid therapies, particularly in individuals with specific mitochondrial genotypes linked to succinylcarnitine metabolism. Taken together, our findings provide evidence that therapeutically enhancing bioenergetic health may reduce the risk of symptomatic AD. Furthermore, monitoring the bioenergetic capacity via blood acylcarnitine measurements can be achieved using existing clinical assays.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Acylcarnitine Profiles; Composite Score; Plasma; Beta; Susceptibility; Metabolism; Oxidation; Memory; Pet
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 16, Issue: 1, Pages: , Article Number: 1910 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Institute of Epidemiology (EPI)
Institute of Experimental Genetics (IEG)
POF-Topic(s) 30205 - Bioengineering and Digital Health
30202 - Environmental Health
30201 - Metabolic Health
Research field(s) Enabling and Novel Technologies
Genetics and Epidemiology
PSP Element(s) G-503891-001
G-504091-003
G-500600-001
G-504000-010
Grants National Institutes of Health/the National Institute of Aging
IXICO Ltd.
GE Healthcare
Fujirebio
Genentech, Inc.
F. Hoffmann-La Roche Ltd
EuroImmun
Eli Lilly and Company
Elan Pharmaceuticals, Inc.
Janssen Alzheimer Immunotherapy Research & Development, LLC.
Johnson & Johnson Pharmaceutical Research & Development LLC.
Pfizer Inc.
Novartis Pharmaceuticals Corporation
Neurotrack Technologies
NeuroRx Research
Meso Scale Diagnostics, LLC.
Merck Co., Inc.
Lundbeck
Lumosity
Eisai Inc.
Cogstate
Araclon Biotech
Alzheimer's Association
AbbVie
National Institute of Biomedical Imaging and Bioengineering
National Institute on Aging
DOD ADNI (Department of Defense)
Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant)
ADNI
State of Bavaria
Alzheimer's Drug Discovery Foundation
Althingi
CereSpir, Inc.
Hjartavernd
Bristol-Myers Squibb Company
NIA Intramural Research Program
Biogen
NIH
BioClinica, Inc.
Piramal Imaging
Servier
Takeda Pharmaceutical Company
NINDS
NIA
CurePSP Foundation
Mayo Foundation
German Federal Ministry of Education and Research (BMBF)
Helmholtz Zentrum Munchen - German Research Center for Environmental Health
Alzheimer's Disease Metabolomics Consortium (National Institute on Aging )
Canadian Institutes of Health Research
Transition Therapeutics
DOI 10.1038/s41467-025-57032-0
WOS ID 001430168800006
Scopus ID 85218675491
PubMed ID 39994231
Erfassungsdatum 2025-03-17
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