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Record W4407877093 · doi:10.1038/s41467-025-57032-0

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

2025· article· en· W4407877093 on OpenAlexfundno aff
Matthias Arnold, Mustafa Büyüközkan, P. Murali Doraiswamy, Kwangsik Nho, Tong Wu, Vilmundur Guðnason, Lenore J. Launer, Rui Wang‐Sattler, Jerzy Adamski, Philip L. De Jager, Nilüfer Ertekin‐Taner, David A. Bennett, Andrew J. Saykin, Annette Peters, Karsten Suhre, Rima Kaddurah‐Daouk, Gabi Kastenmüller, Jan Krumsiek

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMitochondrial Function and Pathology
Canadian institutionsnot available
FundersNational Institute on Drug AbuseNational Institute on AgingHelmholtz Zentrum MünchenCanadian Institutes of Health ResearchNational Institutes of HealthGenentechNational Institute of Neurological Disorders and StrokeIXICONorthern California Institute for Research and EducationHjartaverndCurePSPServierEisaiBundesministerium für Bildung und ForschungH. Lundbeck A/SRush UniversityMayo Foundation for Medical Education and ResearchUniversity of Southern CaliforniaPfizerBioClinicaBiogenU.S. Department of DefenseEli Lilly and CompanyBristol-Myers SquibbMeso Scale DiagnosticsAlzheimer's Disease Neuroimaging InitiativeNovartis Pharmaceuticals CorporationAlzheimer's Association
KeywordsBioenergeticsResilience (materials science)DiseaseAlzheimer's diseaseBiologyNeuroscienceGerontologyMedicineCell biologyPhysicsMitochondrionPathology

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.302
Teacher spread0.283 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations19
Published2025
Admission routes1
Has abstractyes

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Same venueNature CommunicationsSame topicMitochondrial Function and PathologyFrench-language works237,207