Lewy body dementia promotion by air pollutants

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_2.5) exposure raises LBD risk. Mechanistically, we found that PM_2.5 exposure led to brain atrophy in wild-type mice, an effect not seen in α-synuclein (αSyn)-deficient mice. PM_2.5 exposure generated a highly pathogenic αSyn strain, PM_2.5-induced preformed fibril (PM-PFF), with enhanced proteinase K resistance and neurotoxicity, resembling αSyn LBD strains. PM_2.5 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_2.5-exposed mice and LBD patients, underscoring PM_2.5's role in LBD and stressing the need for interventions to reduce air pollution and its associated neurological disease burden.