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This study analyzed five oxidative stress biomarkers in simultaneously collected blood and cerebrospinal fluid samples from 140 adults to determine whether peripheral blood measurements accurately reflect redox status in the central nervous system. Only one biomarker (FRAP) showed positive correlation between compartments, while most markers showed poor or inverse relationships, indicating that blood and CNS oxidative stress measures are largely independent. Advanced statistical analysis revealed that age and sex influence how these biomarkers organize into networks, with older adults and males showing different structural patterns than younger adults and females.
Why it matters
The findings challenge the common practice of using blood samples alone to infer brain oxidative stress status in neurological disease research. This has important implications for designing clinical trials and selecting appropriate biomarkers when studying conditions like Alzheimer's disease, Parkinson's disease, and other CNS disorders where oxidative stress plays a role.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Peripheral blood measurements dominate oxidative stress research, yet whether they reflect central nervous system (CNS) redox status remains untested in humans. We simultaneously profiled five biomarkers, total antioxidant capacity (TAC), glutathione (GSH), thiobarbituric acid-reactive substances (TBARS), ferric reducing antioxidant power (FRAP), and hydroxyl radical scavenging activity (HRSA), in paired blood and cerebrospinal fluid (CSF) from 140 adults in the ALBION cohort. Only FRAP showed a significant positive cross-compartment correlation ({rho} = +0.49, FDR-p < 0.001), supporting its role as a systemic antioxidant signal. TBARS showed a significant inverse cross-compartment association ({rho} = -0.20, FDR-p = 0.042), suggesting compartmental compensation in lipid peroxidation regulation rather than parallel dynamics. TAC and GSH showed no meaningful intercompartmental alignment. Individual biomarker levels were largely stable across the 40-85 year age range in both compartments, suggesting that age effects operate through coordinated latent networks rather than single-marker trajectories. Principal component extraction with varimax rotation identified four latent factors explaining 66.6% of total variance, dominated by a coherent CSF-centred redox axis alongside multiple partially opposing peripheral components. Age stratification revealed progressive fragmentation: middle-aged adults retained four coherent cross-compartment factors, whereas older adults exhibited five more dispersed components. Sex-stratified analyses showed that females exhibited four-factor modular organisation centred on glutathione, while males showed a simpler three-factor structure with tighter cross-compartment coupling anchored by FRAP. Blood and CSF oxidative stress biomarkers are not interchangeable, a finding with direct implications for biomarker selection in clinical trials targeting neurological conditions.
Source: Oxidative Stress Biomarker Profile Dynamics across Blood and Cerebrospinal Fluid