Peripheral inflammation promotes brain tau transmission via disrupting blood–brain barrier

作者：Yanchao Liu, Shujuan Zhang, Xiaoguang Li, Enjie Liu, Xin Wang, Qiuzhi Zhou, Jinwang Ye, Jian‐Zhi Wang · 发表于：Bioscience Reports · 年份：2020 · DOI：10.1042/bsr20193629 · 被引用次数：48 · 研究领域：Alzheimer's disease research and treatments、Neuroinflammation and Neurodegeneration Mechanisms、Barrier Structure and Function Studies

Abnormal aggregation of pathological tau protein is a neuropathological feature of Alzheimer's disease (AD). In the AD patients, the abnormal tau accumulation first appeared in entorhinal cortex (EC) and then propagated to the hippocampus with microglia activation and inflammation, but the mechanism is elusive. Here, we studied the role and mechanisms underlying periphery inflammation on brain tau transmission. By intraperitoneal injection of lipopolysaccharide (LPS) with brain medial entorhinal cortex (MEC)-specific overexpressing P301L human tau (P301L-hTau), we found that both acute and chronic administration of LPS remarkably promoted P301L-hTau transmission from MEC to the hippocampal subsets. Interestingly, the chronic LPS-induced P301L-hTau transmission was still apparent after blocking microglia activation. Further studies demonstrated that LPS disrupted the integrity of blood-brain barrier (BBB) and simultaneous intraperitoneal administration of glucocorticoid (GC) attenuated LPS-promoted P301L-hTau transmission. These data together suggest that a non-microglia-dependent BBB disruption contributes to peripheral LPS-promoted brain P301L-hTau transmission, therefore, maintaining the integrity of BBB can be a novel strategy for preventing pathological tau propagation in AD and other tauopathies.