Differential DNA Methylation in the Brain as Potential Mediator of the Association between Traffic-related PM_2.5 and Neuropathology Markers of Alzheimer's Disease.

ABSTRACT:

Introduction

Growing evidence indicates fine particulate matter (PM_2.5) as risk factor for Alzheimer's' disease (AD), but the underlying mechanisms have been insufficiently investigated. We hypothesized differential DNA methylation (DNAm) in brain tissue as potential mediator of this association.

Methods

We assessed genome-wide DNAm (Illumina EPIC BeadChips) in prefrontal cortex tissue and three AD-related neuropathological markers (Braak stage, CERAD, ABC score) for 159 donors, and estimated donors' residential traffic-related PM_2.5 exposure 1, 3 and 5 years prior to death. We used a combination of the Meet-in-the-Middle approach, high-dimensional mediation analysis, and causal mediation analysis to identify potential mediating CpGs.

Results

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SUBMITTER: Li Z 

PROVIDER: S-EPMC10327281 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature