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PubMed · 40321271

Differential DNA methylation in blood as potential mediator of the association between ambient PM 2.5 and cerebrospinal fluid biomarkers of Alzheimer's disease among a cognitively normal population-based cohort.

Tszshan Ma·Jiaqi Liu·Donghai Liang·Stefanie Ebelt·Kyle Steenland·Allan I Levey·James J Lah·Aliza P Wingo·Thomas S Wingo·Anke Hüls
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Abstract

INTRODUCTION: Fine particulate matter (PM 2.5 ) is a known risk factor for Alzheimer's disease (AD), with emerging evidence linking PM 2.5 exposure to cerebrospinal fluid (CSF) biomarkers in pre-clinical stages. However, the role of DNA methylation (DNAm) as potential mediator in this relationship among cognitively normal individuals remains largely unexplored. METHODS: In 535 cognitively normal individuals, we assessed genome-wide blood DNAm, CSF Aβ 42 concentrations, and residential PM 2.5 exposure in the year preceding blood collection. Multi-stage comprehensive mediation analyses were conducted. RESULTS: Nine CpG sites mediated the PM 2.5 -Aβ42 association, with significant natural indirect effects (NIEs) for eight CpGs, mediating 14-43% of the effect. The joint NIE for all nine CpGs was -0.115 (95% CI: -0.215, -0.101) per 1 ug/m 3 increase in PM 2.5 exposure. Six CpGs are annotated to genes implicated in neuroinflammatory pathways. DISCUSSION: Our findings suggest that differential DNAm, particularly in neuroinflammation-related genes, mediates PM 2.5 toxicity in AD's pre-clinical stage.

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Tszshan Ma, Jiaqi Liu, Donghai Liang, Stefanie Ebelt, Kyle Steenland, Allan I Levey, James J Lah, Aliza P Wingo, Thomas S Wingo, Anke Hüls. 2025-04-16. Differential DNA methylation in blood as potential mediator of the association between ambient PM 2.5 and cerebrospinal fluid biomarkers of Alzheimer's disease among a cognitively normal population-based cohort.. https://doi.org/10.1101/2025.04.15.25325910

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