Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 30:12:1343915.
doi: 10.3389/fpubh.2024.1343915. eCollection 2024.

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

Meijuan Dang  1 , Ye Li  1 , Lili Zhao  1 , Tao Li  1 , Ziwei Lu  1 , Jialiang Lu  1 , Yuxuan Feng  1 , Yang Yang  1 , Fangcun Li  1 , Fan Tang  1 , Xiaoya Wang  1 , Yating Jian  1 , Heying Wang  1 , Lei Zhang  1 , Hong Fan  1 , Guilian Zhang  1
Affiliations

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

Meijuan Dang et al. Front Public Health. .

Abstract

Background: Although 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.

Methods: Drawing 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.

Results: Our 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.

Conclusion: The 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.

Keywords: Alzheimer’s disease; Mendelian randomization; air pollution; neurodegenerative diseases; particulate matter.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Three assumption of MR. (B) The conceptual schematic of the MR research design. IVW, inverse variance weighted; MR-PRESSO, MR pleiotropy residual sum and outlier; PM, particulate matter; SNP, single nucleotide polymorphism.
Figure 2
Figure 2
Forest plot for the effect of PM on AD. CI, confidence interval; MR-PRESSO, MR pleiotropy residual sum and outlier; OR, odds ratio.
Figure 3
Figure 3
(A) Forest plot for the effect of each SNP on AD. (B) Scatter plot for the effect of PM on AD. (C) The overall heterogeneity test of the effect of PM on AD. (D) Leave-one-out to investigate whether the causal association was driven by a unique single SNP.
Figure 4
Figure 4
MVMR for the effect of PM2.5 on AD. CI, confidence interval; OR, odds ratio.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. World Alzheimer Report . Reducing Dementia Risk: Never too early, never too late; (2023).
    1. 2023 Alzheimer's disease facts and figures. Alzheimers Dement. (2023) 19:1598–695. doi: 10.1002/alz.13016 - DOI - PubMed
    1. Murata H, Barnhill LM, Bronstein JM. Air pollution and the risk of Parkinson's disease: a review. Mov Disord. (2022) 37:894–904. doi: 10.1002/mds.28922, PMID: - DOI - PMC - PubMed
    1. Khreis H, Bredell C, Wai Fung K, Hong L, Szybka M, Phillips V, et al. . Impact of long-term air pollution exposure on incidence of neurodegenerative diseases: a protocol for a systematic review and exposure-response meta-analysis. Environ Int. (2022) 170:107596. doi: 10.1016/j.envint.2022.107596, PMID: - DOI - PubMed
    1. Parra KL, Alexander GE, Raichlen DA, Klimentidis YC, Furlong MA. Exposure to air pollution and risk of incident dementia in the UK Biobank. Environ Res. (2022) 209:112895. doi: 10.1016/j.envres.2022.112895, PMID: - DOI - PMC - PubMed

Substances