Extracellular tau clearance is governed by its aggregation state and independent of microglial activation by LPS and IFN-γ

Extracellular tau clearance is governed by its aggregation state and independent of microglial activation by LPS and IFN-γ

Microglia are the tissue resident macrophages of the brain and their contribution to tau pathology progression remains to be fully understood. In this study, we developed a quantitative platform to elucidate the processing of extracellular tau within human induced pluripotent stem cell (iPSC)-derive...

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Bibliographic Details
Main Authors: Andrew Shultz, Anna Vincze, Todd T. Yau, Emma L. Poirier, Hannah Demanche, Jennifer N. Rauch
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:Neurobiology of Disease
Subjects:
Tau
Microglia
Tau spread
LRP1
Endo-lysosomal dysfunction
Inflammation
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996125002748
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Summary:Microglia are the tissue resident macrophages of the brain and their contribution to tau pathology progression remains to be fully understood. In this study, we developed a quantitative platform to elucidate the processing of extracellular tau within human induced pluripotent stem cell (iPSC)-derived microglia. We show that iPSC-derived microglia internalize monomeric and fibrillar tau through different cellular mechanisms and with different clearance kinetics. Acute inflammatory activation of microglia alters tau endocytosis, but surprisingly does not impact tau clearance. These results highlight the importance of the microglial endo-lysosome system as a regulator of tau pathology that is decoupled from acute microglial activation.
ISSN:1095-953X

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