Lewy body dementia promotion by air pollutants
Xiaodi Zhang, 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 J. Denna, S. Zhang, Wenqiang Zheng, Dingli Ye, Xiaoli Rong, Yang Liu, Lili Niu, Han Seok Ko, Weiyi Peng, Lingtao Jin, Mingyao Ying, Liana S. Rosenthal, David W. Nauen, Alexander Pantelyat, Mahima Kaur, Kezia Irene, Liuhua Shi, Rahel Feleke, Sonia García-Ruiz, Mina Ryten, Valina L. Dawson, Francesca Dominici, Rodney J. Weber, Xuan Zhang, Xuan Zhang, Pengfei Liu, Ted M. Dawson, Shizhong Han, Xiaobo Mao
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.