20.500.12556/RUL-181933 Individual bioenergetic capacity as a potential source of resilience to Alzheimer's disease 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. bioenergetic capacity resilience Alzheimer's disease metabolomics bioenergetska zmogljivost odpornost Alzheimerjeva bolezen true false true Angleški jezik Slovenski jezik Članek v reviji 2026-04-20 11:57:09 2026-04-20 11:57:17 2026-04-24 09:57:54 0000-00-00 00:00:00 2025 0 0 15 str. art. 1910 Vol. 16 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 61:577 2041-1723 10.1038/s41467-025-57032-0 264427779 RAZ_Arnold_Matthias_2025.pdf RAZ_Arnold_Matthias_2025.pdf 1 CC304568BD7C096818F8B925B18BE59B 7386471730a40bd21667ca28129fa74de7ff1f28743f4e5a1cf0ce9979b0f393 617a7c99-3e19-11f1-b0ab-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=232897 https://www.nature.com/articles/s41467-025-57032-0 1 1c5ddf9d-3c9f-11f1-b0ab-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=232735 Medicinska fakulteta 0 0 0