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Lewy body dementia promotion by air pollutants

2025/09/04 by Xiaodi Zhang, Haiqing Liu, Xiao Wu +40 · 1 voice · 11 citations
Environmental Science · Health Professions · #Air Quality and Health Impacts #Health, Environment, Cognitive Aging #Noise Effects and Management

paper · doi:10.1126/science.adu4132

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 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.

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