The Exposome-Brain Axis: A Scoping Review of Biological Biomarkers in Environmental Neurotoxicity, Neuroinflammation,...

The escalating global burden of neurodegenerative and neuropsychiatric disorders is deeply intertwined with cumulative environmental toxicant exposure. To accurately capture the prodromal and subclinical impacts of this multi-chemical "pollutome", research is shifting from symptom-based assessments toward the use of objective, quantifiable biological indicators. Guided by the PRISMA-ScR framework, this scoping review systematically analyzed literature across PubMed, Scopus, Web of Science, and Embase databases without temporal restrictions. The final selection included 52 human observational studies that evaluated the relationship between environmental stressors and objective neurobiological markers across diverse geographical populations and life stages. The synthesized evidence reveals that varied environmental insults-including ambient air pollution (e.g., fine particulate matter, PM_2.5), heavy metals, agrochemicals, and persistent organic contaminants-frequently correlate with measurable alterations in fluid biomarkers. These exposures are primarily associated with variations in markers of axonal damage (neurofilament light chain), astrocytic reactivity (glial fibrillary acidic protein), potential microglial dysfunction (soluble triggering receptor expressed on myeloid cells 2), and cytostructural alterations (Tau proteins and amyloid-beta). The literature highlights distinct windows of vulnerability, spanning from early-life epigenetic modifications (DNA methylation) to adult neurovascular injury. Mechanistically, despite their chemical heterogeneity, the available evidence suggests that these pollutants may converge on shared pathophysiological pathways defined by blood-brain barrier disruption and chronic, self-perpetuating neuroinflammation. Understanding environmental neurotoxicity may benefit from moving beyond traditional single-pollutant approaches toward a broader exposome framework. Future epidemiological research should integrate high-dimensional human biomonitoring with artificial intelligence and machine learning architectures. This computational integration would be essential to decode non-linear multi-pollutant interactions and accelerate the deployment of targeted, early-stage public health interventions.