The exposome from neurodevelopment to neurodegeneration: A narrative review

Inspired from the historical debate "nature" versus "nurture", the concept "exposome" recently emerged as a comprehensive framework encompassing the totality of exposures individuals experience, from conception onward, over a complete lifetime, and how they can affect human health. In this narrative review, we present an overview of current knowledge on the exposome, with a particular focus on its impact on brain health across different life stages, highlighting its role during neurodevelopment/childhood, adulthood, physiological aging and neurodegenerative conditions. We explore the three main exposome domains (general external, specific external, internal), underpinning their interconnection. We also provide examples of how specific factors, ranging from chemicals to lifestyle habits, can either positively or negatively influence the CNS structure and function. To this aim, we included articles (mostly between 2005 and 2024) found in open-access databases, selected using the following search terms: "exposome", "central nervous system" and "pregnancy" or "childhood" or "adulthood" or "aging" or "neurodegeneration". Second, we analyzed the relationships between specific exposome domains and each stage of life. Only articles addressing a given risk factor across all life stages were included in the review. In each chapter, we review findings from both human and experimental studies, when available, with an insight on biological mechanisms, in order to link exposure to phenotype. This work highlights the potential of the exposomics' framework to support public health policies and facilitate the prevention and treatment of multifactorial neurological disorders, while underscoring the importance of interdisciplinary efforts to address the multifaceted environmental determinants endangering the CNS health.