Lewy body dementia promotion by air pollutants.

Zhang, Xiaodi; Liu, Haiqing; Wu, Xiao; Jia, Longgang; Gadhave, Kundlik; Wang, Lena; Zhang, Kevin; Li, Hanyu et al. · Science · 2025

basic_science · Level V

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Abstract

Evidence links air pollution to dementia, yet its role in Lewy body dementia (LBD) remains unclear. In this work, we showed in a cohort of 56.5 million individuals across the United States that fine particulate matter (PM<sub>2.5</sub>) exposure raises LBD risk. Mechanistically, we found that PM<sub>2.5</sub> exposure led to brain atrophy in wild-type mice, an effect not seen in α-synuclein (αSyn)-deficient mice. PM<sub>2.5</sub> exposure generated a highly pathogenic αSyn strain, PM<sub>2.5</sub>-induced preformed fibril (PM-PFF), with enhanced proteinase K resistance and neurotoxicity, resembling αSyn LBD strains. PM<sub>2.5</sub> samples from China, the United States, and Europe consistently induced proteinase-resistant αSyn strains and in vivo pathology. Transcriptomic analyses revealed shared responses between PM<sub>2.5</sub>-exposed mice and LBD patients, underscoring PM<sub>2.5</sub>'s role in LBD and stressing the need for interventions to reduce air pollution and its associated neurological disease burden.

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