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.
Zhenjiang LiDonghai LiangStefanie EbeltMarla GearingMichael S KoborChaini KonwarJulie L MaclsaacKristy DeverAliza P WingoAllan I LeveyJames J LahThomas S WingoAnke HülsPublished in: Alzheimer's & dementia : the journal of the Alzheimer's Association (2024)
First study to evaluate the potential mediation effect of DNA methylation for the association between PM2.5 exposure and neuropathological changes of Alzheimer's disease. Study was based on brain tissues rarely investigated in previous air pollution research. Cg10495669, assigned to RBCK1 gene playing a role in inflammation, was associated consistently with 1-year, 3-year, and 5-year traffic-related PM2.5 exposures prior to death. Meet-in-the-middle approach and high-dimensional mediation analysis were used simultaneously to increase the potential of identifying the differentially methylated CpGs. Differential DNAm related to neuroinflammation was found to mediate the association between traffic-related PM2.5 and Alzheimer's disease.
Keyphrases
- human health
- air pollution
- risk assessment
- particulate matter
- dna methylation
- lung function
- heavy metals
- gene expression
- genome wide
- cognitive decline
- white matter
- social support
- resting state
- polycyclic aromatic hydrocarbons
- multiple sclerosis
- depressive symptoms
- lipopolysaccharide induced
- transcription factor
- functional connectivity
- inflammatory response
- blood brain barrier
- subarachnoid hemorrhage