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Identifying the mediating role of inflammation on the relationship between socioeconomic status and Alzheimer’s disease: a Mendelian randomization analysis and mediation analysis

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Abstract

Background and objectives

Observational studies have demonstrated a significant association between socio-economic status (SES) and Alzheimer's disease (AD). Nonetheless, the precise biological mechanisms underlying this association remain unclear. Therefore, we adopted a Mendelian Randomization (MR) approach to investigate the causal relationship between SES and genetic susceptibility to AD, as well as to explore the potential mediation effects of inflammation.

Methods

Large-scale cohorts based on publicly available genome-wide association study (GWAS) datasets from European populations were employed for conducting the MR study. The primary criterion utilized was the inverse-variance weighting (IVW) model. Heterogeneity and horizontal pleiotropy were assessed. In addition, multivariate MR (MVMR) was utilized to correct the confounders. Moreover, a two-step MR approach was used to evaluate the potential mediating effects of factors on the causal effects between SES and AD.

Results

As indicated by the results of the IVW model, educational years (OR = 0.708, 95% CI 0.610–0.821, P < 0.001) and household income (OR = 0.746, 95% CI 0.566–0.982, P = 0.037) was associated with a decreased genetic susceptibility risk for AD. The univariable results showed that the causal effect of educational years on the lower risk of AD remained significant (OR = 0.643, 95% CI 0.467–0.886, P = 0.006). In addition, our findings indicated that C-reactive protein (CRP) played a role in the causal effect of educational years on AD. The proportions of mediation were − 50.08% (95% CI − 92.78; − 7.38%).

Discussion

These findings provided evidence supporting the causal effect of educational attainment lower AD risk, with inflammation playing a mediating role. These findings may inform prevention strategies and interventions directed toward AD. Future studies should explore other plausible biological mechanisms.

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Data availability statement

The original contributions presented in the study are included in the article/Supplementary Material. The dataset generated during and analysed during the current study are available from the MR Base database (http://www.mrbase.org/).

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Acknowledgements

We are grateful to the many participants and researchers for collecting, contributing to the GWAS dataset, and making their GWAS summary statistics publicly available.

Funding

This work was supported by the National Key Research and Development Program of China (2022YFC3602600), National Natural Science Foundation of China (82220108009, 81970996), and STI2030-Major Projects (2021ZD0201801).

Author information

Author notes

  1. Chaofan Geng and Ke Meng have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology and Innovation Center for Neurological Disorders, Xuanwu Hospital, National Center for Neurological Disorders, Capital Medical University, 45 Changchun Street, Beijing, 100053, China

    Chaofan Geng, Ke Meng & Yi Tang

  2. Neurodegenerative Laboratory of Ministry of Education of the People’s Republic of China, Beijing, China

    Yi Tang

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  1. Chaofan Geng
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  2. Ke Meng
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  3. Yi Tang
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Contributions

CG and KM study concept, design, software, and paper writing. KM data curation and software. YT dissertation revision. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yi Tang.

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The authors declare no interest.

Ethical approval

Since all analyses were based on publicly available summary statistics, no patients were involved in the design of the study, and no ethical approval from an institutional review board was required.

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Supplementary file1 (DOCX 416 KB)

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Geng, C., Meng, K. & Tang, Y. Identifying the mediating role of inflammation on the relationship between socioeconomic status and Alzheimer’s disease: a Mendelian randomization analysis and mediation analysis. J Neurol 271, 2484–2493 (2024). https://doi.org/10.1007/s00415-023-12176-1

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