Lewy body dementia promotion by air pollutants
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<sub>2.5</sub>) exposure raises LBD risk. Mechanistically, we found that PM<sub>2.5</sub> exposure led to brain atrophy in wild-type mice, an effect not seen in α-synuclein (αSyn)-deficient mice. PM<sub>2.5</sub> exposure generated a highly pathogenic αSyn strain, PM<sub>2.5</sub>-induced preformed fibril (PM-PFF), with enhanced proteinase K resistance and neurotoxicity, resembling αSyn LBD strains. PM<sub>2.5</sub> 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<sub>2.5</sub>-exposed mice and LBD patients, underscoring PM<sub>2.5</sub>'s role in LBD and stressing the need for interventions to reduce air pollution and its associated neurological disease burden.
Authors
- Bong Gu Kang (ORCID: https://orcid.org/0000-0003-0594-9509)
- Shizhong Han (ORCID: https://orcid.org/0000-0002-5114-6742)
- Ramhari Kumbhar (ORCID: https://orcid.org/0000-0002-8975-2502)
- Francesca Dominici (ORCID: https://orcid.org/0000-0002-9382-0141)
- Rodney J. Weber (ORCID: https://orcid.org/0000-0003-0765-8035)
- David W. Nauen (ORCID: https://orcid.org/0000-0002-2652-9944)
- Bin Bai (ORCID: https://orcid.org/0000-0002-6979-7412)
- Ying Wang (ORCID: https://orcid.org/0000-0002-0259-9147)
- Ma. Cristine Faye J. Denna
- H. Li
- Ted M. Dawson (ORCID: https://orcid.org/0000-0002-6459-0893)
- Valina L. Dawson (ORCID: https://orcid.org/0000-0002-2915-3970)
- S. Zhang (ORCID: https://orcid.org/0000-0001-6816-0172)
- Han Seok Ko
- Sonia García-Ruiz (ORCID: https://orcid.org/0000-0003-4913-5312)
- Xiaobo Mao (ORCID: https://orcid.org/0000-0001-6587-556X)
- Wenqiang Zheng (ORCID: https://orcid.org/0000-0002-3357-1075)
- Pengfei Liu (ORCID: https://orcid.org/0000-0001-7280-9720)
- Liuhua Shi (ORCID: https://orcid.org/0000-0001-8165-4644)
- Dingli Ye
- Mina Ryten (ORCID: https://orcid.org/0000-0001-9520-6957)
- Alexander Pantelyat (ORCID: https://orcid.org/0000-0002-6427-7485)
- Minhan Park (ORCID: https://orcid.org/0000-0002-7289-4053)
- Liana S. Rosenthal (ORCID: https://orcid.org/0000-0001-5140-3967)
- Xiaodi Zhang (ORCID: https://orcid.org/0000-0001-5452-4027)
- Mahima Kaur (ORCID: https://orcid.org/0000-0001-7147-4084)
- Kundlik Gadhave (ORCID: https://orcid.org/0000-0003-4530-4772)
- Lili Niu (ORCID: https://orcid.org/0000-0002-8865-1654)
- Weiyi Peng (ORCID: https://orcid.org/0000-0002-7785-6240)
- Xiao Wu (ORCID: https://orcid.org/0000-0002-4884-657X)
- Yang Liu (ORCID: https://orcid.org/0000-0003-1467-2652)
- Mingyao Ying (ORCID: https://orcid.org/0000-0002-6215-4959)
- Xiaoli Rong (ORCID: https://orcid.org/0000-0002-1030-509X)
- Chantelle E. Terrillion (ORCID: https://orcid.org/0009-0005-9266-8845)
- Rahel Feleke (ORCID: https://orcid.org/0000-0003-2873-7525)
- Longgang Jia (ORCID: https://orcid.org/0000-0003-3400-5531)
- Kezia Irene (ORCID: https://orcid.org/0000-0003-4719-2639)
- Ning Wang (ORCID: https://orcid.org/0000-0002-3410-8509)
- Rong Chen (ORCID: https://orcid.org/0000-0001-9291-5539)
- Guomin Zhang (ORCID: https://orcid.org/0000-0002-3503-7431)
- Xuan Zhang (ORCID: https://orcid.org/0000-0003-1548-8021)
- Haiqing 海庆 LIU 刘 (ORCID: https://orcid.org/0000-0001-5721-0728)
- Lingtao Jin (ORCID: https://orcid.org/0009-0005-8106-3250)
Institutions
- Kennedy Krieger Institute (US)
- Georgia Institute of Technology (US)
- Harvard University (US)
- Johns Hopkins University (US)
- University of California, Merced (US)
- The University of Texas at San Antonio Health Science Center (US)
- University of Cambridge (GB)
- Johns Hopkins Medicine (US)
- UK Dementia Research Institute (GB)
- Institute of Child Health (IN)
- Lieber Institute for Brain Development (US)
- University of Houston (US)
- University College London (GB)
- Imperial College London (GB)
- Vertex Pharmaceuticals (United States) (US)
- Columbia University (US)
Publication Details
- Journal
- Science
- Published
- 2025-09-04
- DOI
- https://doi.org/10.1126/science.adu4132
- Citations
- 20
- Primary Topic
- Air Quality and Health Impacts
- Type
- article
- Field-Weighted Citation Impact
- 23.99