ArticleAging cell2025
DNA Methylation Signatures of Systemic Inflammation Are Associated With Brain Volume, Cognitive Trajectories, and Long-Term Dementia Risk.
Article in Aging cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- The GrimAge clock corresponds to brain ageing and social determinants of health in people with HIV.EBioMedicine · 2026Article
- Long-term risk of dementia following encephalitis: a large-scale retrospective cohort study of electronic health records.Journal of neurology · 2026Article
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Authors and funding
21 authors.
Funding
Abstract
C-reactive protein (CRP) and growth differentiation factor 15 (GDF15) are important markers of inflammation associated with brain health. Compared to plasma, DNA methylation (DNAm) measures of CRP and GDF15 may provide stable epigenetic measures of chronic exposure to inflammation and could therefore be robustly predictive of inflammation-related brain aging and neurodegeneration. We leveraged a subsample of Baltimore Longitudinal Study of Aging (BLSA) participants with DNAm/plasma data and longitudinal neuroimaging/cognition data (n = 430-1100). We used a proteome-wide analysis to characterize the biology of DNAm CRP and GDF15, and latent growth curve models to explore the associations with longitudinal trajectories of 19 brain region volumes and five cognitive domains. Finally, we related DNAm/plasma CRP and GDF15 to dementia risk in two external cohorts. DNAm CRP and GDF15 showed a proteomic signature consistent with systemic immune activation. We identified several brain regions with significant associations between elevated DNAm CRP And GDF15 and (a) lower brain volume level (at age 75) and (b) greater rate of atrophy. Compared to plasma CRP, DNAm CRP was more strongly associated with brain volume, cognitive trajectories, and dementia risk. DNAm and plasma GDF15 were similarly associated with several total lobar, total lobar white matter, and AD-relevant region trajectories and dementia risk, but DNAm measures outperformed plasma measures in relation to cognitive trajectories. Epigenetic signatures of CRP and GDF15 reflect immune and inflammation-related pathway activation. These signatures, especially DNAm CRP, were associated with accelerated brain atrophy, cognitive decline, as well as long-term dementia risk.
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Registered trials
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