Faculty, Staff and Student Publications

Language

English

Publication Date

9-4-2025

Journal

Science

DOI

10.1126/science.adu4132

PMID

40906862

PMCID

PMC12459341

PubMedCentral® Posted Date

9-25-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Evidence links air pollution to dementia, yet its role in Lewy body dementia (LBD) remains unclear. Here we showed in a cohort of 56.5 million individuals across the U.S. that PM2.5 exposure raises LBD risk. Mechanistically, we found PM2.5 exposure led to brain atrophy in wild-type mice, an effect not seen in α-synuclein (αSyn)-deficient mice. PM2.5 exposure generated 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 induced proteinase-resistant αSyn strains and in vivo pathology. Transcriptomic analyses revealed 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.

Keywords

Aged, Animals, Female, Humans, Male, Mice, Air Pollutants, Air Pollution, alpha-Synuclein, Atrophy, Brain, China, Lewy Body Disease, Particulate Matter, United States, Environmental Exposure, Incidence

Published Open-Access

yes

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