Lewy body dementia promotion by air pollutants

• 成果类型: Article
• 署名作者: 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; Garcia-Ruiz, Sonia; Ryten, Mina; Dawson, Valina L.; Dominici, Francesca; Weber, Rodney J.; Zhang, Xuan; Liu, Pengfei; Dawson, Ted M.; Han, Shizhong; Mao, Xiaobo
• 署名单位: Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Columbia University; Johns Hopkins University; Johns Hopkins Medicine; University System of Georgia; Georgia Institute of Technology; University of Houston System; University of Houston; University of Texas System; University of Texas at San Antonio; Johns Hopkins University; Johns Hopkins Medicine; Harvard University; Harvard T.H. Chan School of Public Health; Vertex Pharmaceuticals; Imperial College London; University of Cambridge; University of Cambridge; University of London; University College London; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; University of California System; University of California Merced; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Johns Hopkins Medicine; Johns Hopkins University; Tianjin University of Science & Technology
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adu4132
• 发表日期: 2025-09-04
• 页码: eadu4132
• 关键词: alpha-synuclein; parkinsons-disease; cognitive impairment; atrophy; pm2.5; alzheimers; dysfunction; population; biomarkers; fibrils

摘要

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 alpha-synuclein (alpha Syn)-deficient mice. PM2.5 exposure generated a highly pathogenic alpha Syn strain, PM2.5-induced preformed fibril (PM-PFF), with enhanced proteinase K resistance and neurotoxicity, resembling alpha Syn LBD strains. PM2.5 samples from China, the United States, and Europe consistently induced proteinase-resistant alpha Syn 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.