Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.
Research Center for Environment and Health, Zhongnan University of Economics and Law, Wuhan, China.
JCI Insight. 2024 Jul 22;9(14):e176703. doi: 10.1172/jci.insight.176703.
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.
tau 的聚集和类朊病毒传播是阿尔茨海默病 (AD) 和其他 tau 病的标志。然而，tau 病理学组装和传播的分子机制仍难以捉摸。流行病学数据表明，暴露于细颗粒物 (PM2.5) 会增加患 AD 的风险。然而，其分子机制尚不清楚。在这里，我们表明 PM2.5 触发了 tau 的聚集并促进了 tau 纤维的形成。将 PM2.5 诱导的 tau 预形成纤维 (PFF) 注射到 tau P301S 转基因小鼠的海马体中，促进了 tau 的聚集，并导致认知缺陷和突触功能障碍。此外，PM2.5 的鼻腔内给药加剧了 tau 病理学，并导致 tau P301S 小鼠的认知障碍。总之，我们的结果表明，PM2.5 暴露促进了 tau 病理学并导致认知障碍。这些结果为 PM2.5 如何增加 AD 的风险提供了机制上的见解。
