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Peripheral inflammation promotes brain tau transmission via disrupting blood-brain barrier.

ABSTRACT: 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.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7033313 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Peripheral inflammation promotes brain tau transmission via disrupting blood-brain barrier.

Liu Yanchao Y Zhang Shujuan S Li Xiaoguang X Liu Enjie E Wang Xin X Zhou Qiuzhi Q Ye Jinwang J Wang Jian-Zhi JZ

Bioscience reports 20200201 2

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 ...[more]

PMID: 32043530

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Dataset Information

Peripheral inflammation promotes brain tau transmission via disrupting blood-brain barrier.

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Peripheral inflammation promotes brain tau transmission via disrupting blood-brain barrier.

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