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

Arnold, Matthias (author), Adamski, Jerzy (author), Krumsiek, Jan (author)

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.

• Language: English
• Keywords: bioenergetic capacity, resilience, Alzheimer's disease, metabolomics
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 15 str.
• Numbering: Vol. 16, art. 1910
• PID: 20.500.12556/RUL-181933
• UDC: 61:577
• ISSN on article: 2041-1723
• DOI: 10.1038/s41467-025-57032-0
• COBISS.SI-ID: 264427779
• Publication date in RUL: 20.04.2026

Record is a part of a journal

• Title: Nature communications
• Shortened title: Nat. Commun.
• Publisher: Nature Publishing Group
• ISSN: 2041-1723
• COBISS.SI-ID: 2315876

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: bioenergetska zmogljivost, odpornost, Alzheimerjeva bolezen