| Author |
Zhang X, Liu H, Wu X, Jia L, Gadhave K, Wang L, Zhang K, Li H, Chen R, Kumbhar R, Wang N, Terrillion CE, Kang BG, Bai B, Park M, Denna MCF, Zhang S, Zheng W, Ye D, Rong X, Yang L, Niu L, Ko HS, Peng W, Jin L, Ying M, Rosenthal LS, Nauen DW, Pantelyat A, Kaur M, Irene K, Shi L, Feleke R, García-Ruiz S, Ryten M, Dawson VL, Dominici F, Weber RJ, Zhang X, Liu P, Dawson TM, Han S, Mao X.
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| 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 (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 α-synuclein (αSyn)-deficient mice. PM2.5 exposure generated a highly pathogenic αSyn strain, PM2.5-induced preformed fibril (PM-PFF), with enhanced proteinase K resistance and neurotoxicity, resembling αSyn LBD strains. PM2.5 samples from China, the United States, and Europe consistently induced proteinase-resistant αSyn strains and in vivo pathology. Transcriptomic analyses revealed shared responses between 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.
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