Alterations in neuroinflammatory and neurodegenerative biomarkers among long-term residents of a critically polluted area: a cross-sectional comparative study

Ambient air pollution is increasingly recognized as an emerging risk factor for neurodegenerative diseases. However, evidence from community-based biomarker studies in highly polluted Indian regions remains sparse. To investigate the neuroinflammatory and neurodegenerative effects of chronic exposure to ambient air pollutants in long-term residents of a critically polluted area compared to a control region. This cross-sectional study included 203 adults (aged 40-60) residentially exposed to critical levels of air pollutants for ≥ 10 years and 202 geo-demographically matched controls residing at locations with very low / minimal air pollution. Air pollutant levels across all seasons were measured according standard protocols. Blood samples were analyzed for neurological biomarkers (viz. Aβ_1-42, Total Tau, α-Synuclein, brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP) using ELISA. Additionally, demographic, clinical (blood pressure, random blood sugar, lipid profile) and occupational data were collected. Appropriate, descriptive, comparative and regression statistics were applied after checking for the normality. Annual PM_2.5 and ozone concentrations were significantly higher at the exposed site (PM_2.5: 69.76 ± 15.99 µg/m³; ozone: 33.76 ± 11.58 µg/m³) compared to controls (p < 0.001). Exposed participants showed significantly elevated GFAP (p < 0.001) and Aβ_1-42 (p = 0.044), and significantly reduced levels of total tau, α-synuclein, and BDNF (p < 0.001), suggesting glial activation and impaired neuroprotection. Regression analyses confirmed exposure as a key predictor of biomarker variance, independent of age, BMI, blood pressure, and lipid levels. Chronic exposure to critical levels of ambient air pollutant is associated with subclinical alterations in neuroinflammatory and neurodegenerative plasma biomarkers. These findings underscore the potential for air pollution to contribute to neurological dysfunction and support the need for public health interventions and longitudinal studies. Further, plasma-based biomarkers replicated results previously reported using cerebrospinal fluid (CSF) and post-mortem tissue samples, thereby enabled minimally invasive detection of neurobiological alterations at the community level, supporting their potential utility in population-level environmental health research.