Lewy body dementia promotion by air pollutants

IF 45.8 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2025-09-04 DOI:10.1126/science.adu4132

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

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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 (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.

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空气污染物促进路易体痴呆

有证据表明空气污染与痴呆症有关，但它在路易体痴呆（LBD）中的作用尚不清楚。在这项工作中，我们在美国5650万人的队列中显示，细颗粒物（PM2.5）暴露会增加LBD的风险。在机制上，我们发现PM2.5暴露会导致野生型小鼠脑萎缩，而α-突触核蛋白（αSyn）缺陷小鼠则没有这种影响。PM2.5暴露产生高致病性αSyn菌株，PM2.5诱导的预成型纤维（PM-PFF），具有增强的蛋白酶K抗性和神经毒性，类似于αSyn LBD菌株。来自中国、美国和欧洲的PM2.5样品一致诱导了蛋白酶抗性αSyn菌株和体内病理。转录组学分析揭示了PM2.5暴露小鼠和LBD患者之间的共同反应，强调了PM2.5在LBD中的作用，并强调了采取干预措施减少空气污染及其相关神经系统疾病负担的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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