Science (New York, N.Y.)
Published

Lewy body dementia promotion by air pollutants

Authors

Xiaodi Zhang, Haiqing Liu, Xiao Wu, Longgang Jia, Kundlik Gadhave, Lena Wang, Kevin Zhang, Hanyu Li, Rong Chen, Ramhari Kumbhar, Ning Wang, Chantelle E Terrillion, Bong Gu Kang, Bin Bai, Minhan Park, Ma Cristine Faye Denna, Shu Zhang, Wenqiang Zheng, Denghui Ye, Xiaoli Rong, Liu Yang, Lili Niu, Han Seok Ko, Weiyi Peng, Lingtao Jin, Mingyao Ying, Liana S Rosenthal, David W Nauen, Alex Pantelyat, Mahima Kaur, Kezia Irene, Liuhua Shi, Rahel Feleke, Sonia García-Ruiz, Mina Ryten, Valina L Dawson, Francesca Dominici, Rodney J Weber, Xuan Zhang, Pengfei Liu, Ted M Dawson, Shizhong Han, Xiaobo Mao
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Abstract

Science. 2025 Sep 4;389(6764):eadu4132. doi: 10.1126/science.adu4132. Epub 2025 Sep 4.

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 (PM2.5) exposure raises LBD risk. Mechanistically, we found that 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, PM2.5-induced preformed fibril (PM-PFF), with enhanced proteinase K resistance and neurotoxicity, resembling αSyn LBD strains. PM2.5 samples from China, the United States, and Europe consistently induced proteinase-resistant αSyn strains and in vivo pathology. Transcriptomic analyses revealed shared responses between PM2.5-exposed mice and LBD patients, underscoring PM2.5's role in LBD and stressing the need for interventions to reduce air pollution and its associated neurological disease burden.

PMID:40906862 | DOI:10.1126/science.adu4132

UK DRI Authors

Mina Ryten

Prof Mina Ryten

Centre Director

Leveraging brain transcriptomics to understand the pathophysiology of Lewy body diseases

Prof Mina Ryten