Lewy body dementia promotion by air pollutants
- 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
2025-09-04
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.