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An epigenetic proxy of chronic inflammation outperforms serum levels as a biomarker of brain ageing

By Eleanor LS Conole, Anna J Stevenson, Claire Green, Sarah E Harris, Susana Munoz-Maniega, María del. C Valdés-Hernández, Mathew A Harris, Mark Bastin, Joanna Wardlaw, Ian J Deary, Veronique E. Miron, Heather Whalley, Riccardo E Marioni, Simon R Cox

Posted 13 Oct 2020
medRxiv DOI: 10.1101/2020.10.08.20205245

Low-level chronic inflammation increases with age and is associated with cognitive decline. DNA methylation (DNAm) levels may provide more stable reflections of cumulative inflammatory burden than traditional serum approaches. Using structural and diffusion MRI data from 521 individuals aged 73, we demonstrate that a DNAm proxy of C-Reactive Protein (CRP) shows significantly (on average 6.4-fold) stronger associations with brain structural outcomes than serum CRP. We additionally find that DNAm CRP has an inverse association with global and domain-specific (speed, visuospatial and memory) cognitive functioning, and that brain structure partially mediates this CRP-cognitive association (up to 29.4%), dependent on lifestyle and health factors. These data support the hypothesis that chronic systemic inflammation may contribute to neurodegenerative brain changes which underlie differences in cognitive ability in later life. DNA methylation-based predictors could be used as proxies for chronic inflammatory status.

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