Lewy body dementia promotion by air pollutants

Evidence links air pollution to dementia, yet its role in Lewy body dementia (LBD) remains unclear. Here we show in a cohort of 56.5 million individuals across the U.S. that PM2.5 exposure significantly raises LBD risk. Mechanistically, we find PM2.5 exposure leads to brain atrophy in wild-type mice, an effect not seen in α-synuclein (αSyn)-deficient mice. PM2.5 exposure generates a highly pathogenic αSyn strain, PM-PFF, with enhanced proteinase K-resistance and neurotoxicity, resembling αSyn LBD strains. PM2.5 samples from China, the U.S., and Europe consistently induce proteinase-resistant αSyn strains and in vivo pathology. Transcriptomic analyses reveal shared responses between PM2.5-exposed mice and LBD patients, underscoring PM2.5’s role in LBD and the stresses the need for interventions to reduce air pollution and its associated neurological disease burden.