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Assessing the contribution of the chemical exposome to neurodegenerative disease

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Abstract

Over the past few decades, numerous environmental chemicals from solvents to pesticides have been suggested to be involved in the development and progression of neurodegenerative diseases. Most of the evidence has accumulated from occupational or cohort studies in humans or laboratory research in animal models, with a range of chemicals being implicated. What has been missing is a systematic approach analogous to genome-wide association studies, which have identified dozens of genes involved in Alzheimer’s disease, Parkinson’s disease and other neurodegenerative diseases. Fortunately, it is now possible to study hundreds to thousands of chemical features under the exposome framework. This Perspective explores how advances in mass spectrometry make it possible to generate exposomic data to complement genomic data and thereby better understand neurodegenerative diseases.

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Fig. 1: The chemical exposome of neurodegenerative diseases: from epidemiological concept to implementation.
Fig. 2: Cellular and molecular pathways affected by chemical pollutants in AD and PD neurodegenerative diseases.

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Acknowledgements

S.L.-A., J.C., F.M., A.D. and C.S. were funded by a grant from the ‘Fondation pour la Recherche Medicale’ (ENV202003011520). They acknowledge L. Rieusset for her contribution to this work. C.S. also received research support from the ‘Fondation de France’ (00130155). C.S. acknowledges the Precision and global Vascular Brain Health Institute funded by the France 2030 investment plan (Instituts Hospitalo-Universitaires vague 3, IHU3 initiative). J.C., F.M., X.C., R.B. and A.D. acknowledge the research infrastructure France Exposome.

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  1. These authors contributed equally: S. Lefèvre-Arbogast, J. Chaker.

  2. These authors jointly supervised this work: A. David, C. Samieri.

Authors and Affiliations

  1. University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, Bordeaux, France

    S. Lefèvre-Arbogast & C. Samieri

  2. Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Rennes, France

    S. Lefèvre-Arbogast, J. Chaker, F. Mercier & A. David

  3. Université Paris Cité, T3S, INSERM UMR-S 1124, Paris, France

    R. Barouki & X. Coumoul

  4. Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA

    G. W. Miller

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Lefèvre-Arbogast, S., Chaker, J., Mercier, F. et al. Assessing the contribution of the chemical exposome to neurodegenerative disease. Nat Neurosci 27, 812–821 (2024). https://doi.org/10.1038/s41593-024-01627-1

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