Zhang Xiaodi, Liu Haiqing, Wu Xiao, Jia Longgang, Gadhave Kundlik, Wang Lena, Zhang Kevin, Li Hanyu, Chen Rong, Kumbhar Ramhari, Wang Ning, Terrillion Chantelle E, Kang Bong Gu, Bai Bin, Park Minhan, Denna Ma Cristine Faye, Zhang Shu, Zheng Wenqiang, Ye Denghui, Rong Xiaoli, Yang Liu, Niu Lili, Ko Han Seok, Peng Weiyi, Jin Lingtao, Ying Mingyao, Rosenthal Liana S, Nauen David W, Pantelyat Alex, Kaur Mahima, Irene Kezia, Shi Liuhua, Feleke Rahel, García-Ruiz Sonia, Ryten Mina, Dawson Valina L, Dominici Francesca, Weber Rodney J, Zhang Xuan, Liu Pengfei, Dawson Ted M, Han Shizhong, Mao Xiaobo
Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Science. 2025 Sep 4;389(6764):eadu4132. doi: 10.1126/science.adu4132.
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) exposure raises LBD risk. Mechanistically, we found that PM exposure led to brain atrophy in wild-type mice, an effect not seen in α-synuclein (αSyn)-deficient mice. PM exposure generated a highly pathogenic αSyn strain, PM-induced preformed fibril (PM-PFF), with enhanced proteinase K resistance and neurotoxicity, resembling αSyn LBD strains. PM 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-exposed mice and LBD patients, underscoring PM's role in LBD and stressing the need for interventions to reduce air pollution and its associated neurological disease burden.
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