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.