The article "Assessing the Contribution of the Chemical Exposome to Neurodegenerative Disease" by S. Lefevre-Arbogast et al. explores the role of environmental chemicals in the development and progression of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). The authors highlight the need for a systematic approach to study chemical exposomes, similar to genome-wide association studies that have identified genetic factors in these diseases. Advances in mass spectrometry have enabled the generation of exposomic data, which can complement genomic data to better understand neurodegenerative diseases. The article reviews epidemiological and experimental evidence linking various chemical exposures to neurodegenerative diseases, focusing on pollutants from anthropogenic activities. It discusses the challenges in studying chemical exposures, including the complexity of exposure routes, the long latency period of these diseases, and the need for high-throughput molecular approaches to profile the internal chemical exposome. Key findings include the strong association between occupational exposure to pesticides and PD, and a lesser but significant association with AD. The article also emphasizes the importance of metals, solvents, and fine particulate matter (PM2.5) in neurodegenerative diseases, with PM2.5 being linked to an increased risk of dementia, AD, and PD. The impact of chemical stressors on neurodegenerative pathways, such as oxidative stress and mitochondrial dysfunction, is discussed, along with the emerging role of neuroinflammation. The authors identify gaps in current research, such as the lack of studies on non-persistent pesticides and synthetic additive chemicals, and propose a roadmap for future research. They advocate for the integration of exposomics with other omics layers to provide a comprehensive understanding of the environmental factors contributing to neurodegenerative diseases. The article concludes by highlighting the potential of high-resolution mass spectrometry (HRMS) to advance exposomic studies and identify chemical signatures associated with these diseases.The article "Assessing the Contribution of the Chemical Exposome to Neurodegenerative Disease" by S. Lefevre-Arbogast et al. explores the role of environmental chemicals in the development and progression of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). The authors highlight the need for a systematic approach to study chemical exposomes, similar to genome-wide association studies that have identified genetic factors in these diseases. Advances in mass spectrometry have enabled the generation of exposomic data, which can complement genomic data to better understand neurodegenerative diseases. The article reviews epidemiological and experimental evidence linking various chemical exposures to neurodegenerative diseases, focusing on pollutants from anthropogenic activities. It discusses the challenges in studying chemical exposures, including the complexity of exposure routes, the long latency period of these diseases, and the need for high-throughput molecular approaches to profile the internal chemical exposome. Key findings include the strong association between occupational exposure to pesticides and PD, and a lesser but significant association with AD. The article also emphasizes the importance of metals, solvents, and fine particulate matter (PM2.5) in neurodegenerative diseases, with PM2.5 being linked to an increased risk of dementia, AD, and PD. The impact of chemical stressors on neurodegenerative pathways, such as oxidative stress and mitochondrial dysfunction, is discussed, along with the emerging role of neuroinflammation. The authors identify gaps in current research, such as the lack of studies on non-persistent pesticides and synthetic additive chemicals, and propose a roadmap for future research. They advocate for the integration of exposomics with other omics layers to provide a comprehensive understanding of the environmental factors contributing to neurodegenerative diseases. The article concludes by highlighting the potential of high-resolution mass spectrometry (HRMS) to advance exposomic studies and identify chemical signatures associated with these diseases.