Ambient particulate matter (PM2.5) exposure contributes to neurodegeneration through the microbiome-gut-brain axis: Therapeutic role of melatonin

Panda, Samir Ranjan; Chaudhari, Vishal Balu; Ahmed, Sahabuddin; Kwatra, Mohit; Jala, Aishwarya; Ponneganti, Srikanth; Pawar, Sharad D.; Borkar, Roshan M.; Sharma, Pawan; Naidu, V.G.M.

doi:10.1016/j.etap.2023.104183

Cited by 10 publications

(1 citation statement)

References 42 publications

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“…Evidence from clinical studies indicate that PM2.5 is associated with AD biomarkers, such as decreased brain-derived neurotrophic factor and elevated tau, in cerebrospinal fluid ( 32 , 33 ). Moreover, recent studies have highlighted the impact of PM on gut microbiome homeostasis, which may give rise to neuroinflammation and neurodegenerative conditions ( 34 ). Another study has reported that PM exposure triggers systemic inflammation, neuroinflammation, and an increased metal load, thus collectively impairing glymphatic clearance efficiency.…”

Section: Discussionmentioning

confidence: 99%

Causal association between particulate matter 2.5 and Alzheimer’s disease: a Mendelian randomization study

Dang,

Li,

Zhao

et al. 2024

Front. Public Health

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BackgroundAlthough epidemiological evidence implies a link between exposure to particulate matter (PM) and Alzheimer’s disease (AD), establishing causality remains a complex endeavor. In the present study, we used Mendelian randomization (MR) as a robust analytical approach to explore the potential causal relationship between PM exposure and AD risk. We also explored the potential associations between PM exposure and other neurodegenerative diseases.MethodsDrawing on extensive genome-wide association studies related to PM exposure, we identified the instrumental variables linked to individual susceptibility to PM. Using summary statistics from five distinct neurodegenerative diseases, we conducted two-sample MR analyses to gauge the causal impact of PM on the risk of developing these diseases. Sensitivity analyses were undertaken to evaluate the robustness of our findings. Additionally, we executed multivariable MR (MVMR) to validate the significant causal associations identified in the two-sample MR analyses, by adjusting for potential confounding risk factors.ResultsOur MR analysis identified a notable association between genetically predicted PM2.5 (PM with a diameter of 2.5 μm or less) exposure and an elevated risk of AD (odds ratio, 2.160; 95% confidence interval, 1.481 to 3.149; p < 0.001). A sensitivity analysis supported the robustness of the observed association, thus alleviating concerns related to pleiotropy. No discernible causal relationship was identified between PM and any other neurodegenerative diseases. MVMR analyses—adjusting for smoking, alcohol use, education, stroke, hearing loss, depression, and hypertension—confirmed a persistent causal relationship between PM2.5 and AD. Sensitivity analyses, including MR-Egger and weighted median analyses, also supported this causal association.ConclusionThe present MR study provides evidence to support a plausible causal connection between PM2.5 exposure and AD. The results emphasize the importance of contemplating air quality interventions as a public health strategy for reducing AD risk.

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Section: Discussionmentioning

confidence: 99%