PM2.5 triggers tau aggregation in a mouse model of tauopathy
Congcong Liu, Lanxia Meng, Yan Gao, Jiehui Chen, Min Zhu, Min Xiong, Tingting Xiao, Xiaoling Gu, Chaoyang Liu, Tao Li, Zhentao Zhang
Congcong Liu, Lanxia Meng, Yan Gao, Jiehui Chen, Min Zhu, Min Xiong, Tingting Xiao, Xiaoling Gu, Chaoyang Liu, Tao Li, Zhentao Zhang
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Research Article Neuroscience

PM2.5 triggers tau aggregation in a mouse model of tauopathy

Abstract

The aggregation and prion-like propagation of tau are the hallmarks of Alzheimer’s disease (AD) and other tauopathies. However, the molecular mechanisms underlying the assembly and spread of tau pathology remain elusive. Epidemiological data show that exposure to fine particulate matter (PM2.5) is associated with an increased risk of AD. However, the molecular mechanisms remain unknown. Here, we showed that PM2.5 triggered the aggregation of tau and promoted the formation of tau fibrils. Injection of PM2.5-induced tau preformed fibrils (PFFs) into the hippocampus of tau P301S transgenic mice promoted the aggregation of tau and induced cognitive deficits and synaptic dysfunction. Furthermore, intranasal administration of PM2.5 exacerbated tau pathology and induced cognitive impairment in tau P301S mice. In conclusion, our results indicated that PM2.5 exposure promoted tau pathology and induced cognitive impairments. These results provide mechanistic insight into how PM2.5 increases the risk of AD.

Authors

Congcong Liu, Lanxia Meng, Yan Gao, Jiehui Chen, Min Zhu, Min Xiong, Tingting Xiao, Xiaoling Gu, Chaoyang Liu, Tao Li, Zhentao Zhang

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Figure 1

Fine particulate matter (PM2.5) promotes tau aggregation in vitro.

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Fine particulate matter (PM2.5) promotes tau aggregation in vitro. (A) T...
(A) The kinetics of tau aggregation in the presence of different concentrations of PM2.5. AFU, arbitrary fluorescence units. n = 7 biologically independent experiments. (B and C) The ultrastructure of tau preformed fibrils (PFFs) and PM2.5-tau PFFs. (B) Transmission electron microscopy (TEM) analysis. Scale bar: 100 nm. (C) Quantitation of the lengths of the fibrils. n = 20 randomly selected images from 6 independent biological experiments. (D and E) PK digestion of tau PFFs and PM2.5-tau PFFs. (D) Equal amounts of tau PFFs and PM2.5-tau PFFs were incubated with 4 μg/mL PK, then analyzed by Coomassie blue staining. (E) The bar graph shows the quantification of the remaining tau species relative to control. n = 6 biologically independent experiments. (F) Tau aggregation kinetics induced by 5% tau PFFs and PM2.5-tau PFFs. n = 7 biologically independent experiments. (G and H) Tau-HEK293 cells were pretreated with different concentrations of PM2.5 for 24 hours, then transduced with tau PFFs. (G) Shown are insoluble tau aggregates at 48 hours after transduction. Scale bar: 20 μm. (H) Quantification of insoluble tau aggregates. n = 6 independent biological experiments (each point represents the average of 10 random fields from each experiment). (I and J) Primary neurons were pretreated with PM2.5 for 24 hours, then transduced with tau PFFs. (I) Shown are p-tau (AT8) staining at 10 days after transduction. Scale bar: 20 μm. AU, arbitrary units. (J) Quantification of AT8 fluorescence intensity. n = 6 independent biological experiments (each point represents the average of 10 random fields from each experiment). Data are presented as mean ± SEM. P values were determined by Student’s t test (C), 2-way ANOVA followed by Holm-Šídák multiple comparisons test (E), or 1-way ANOVA followed by Tukey’s multiple comparisons test (H and J).