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Published on: May 23, 2019
PM2.5 triggers tau aggregation in a mouse model of tauopathy
Congcong Liu1, Lanxia Meng1, Yan Gao1
1Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.
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.
Insights
Fine particulate matter (PM2.5) exposure triggers tau protein aggregation, a key factor in Alzheimer's disease (AD). This study reveals PM2.5 exacerbates tau pathology and cognitive decline in mouse models, linking air pollution to AD risk.
Area of Science:
- Neuroscience
- Environmental Health
- Toxicology
Background:
- Tau aggregation and prion-like propagation are central to Alzheimer's disease (AD) and tauopathies.
- The molecular mechanisms driving tau pathology and its spread are not fully understood.
- Epidemiological studies link fine particulate matter (PM2.5) exposure to increased AD risk, but the underlying mechanisms are unknown.
Purpose of the Study:
- To investigate the molecular mechanisms by which PM2.5 influences tau aggregation and propagation.
- To determine if PM2.5 exposure exacerbates tau pathology and cognitive deficits in a mouse model of tauopathy.
Main Methods:
- In vitro studies assessing PM2.5's effect on tau aggregation and fibril formation.
- In vivo experiments involving hippocampal injection of PM2.5-induced tau preformed fibrils (PFFs) in tau P301S transgenic mice.
- Intranasal administration of PM2.5 to tau P301S mice to assess cognitive function and tau pathology.
Main Results:
- PM2.5 exposure was shown to trigger tau aggregation and promote the formation of tau fibrils.
- Injection of PM2.5-induced tau PFFs into the hippocampus of tau P301S mice led to increased tau aggregation, cognitive deficits, and synaptic dysfunction.
- Intranasal PM2.5 administration worsened tau pathology and induced cognitive impairment in tau P301S mice.
Conclusions:
- PM2.5 exposure promotes tau pathology, including aggregation and fibril formation.
- PM2.5 exposure induces cognitive impairments and synaptic dysfunction, potentially through exacerbating tau pathology.
- These findings provide a mechanistic link between PM2.5 air pollution and an increased risk of Alzheimer's disease.
