Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody

Wenjie Luo, Wencheng Liu, Xiaoyan Hu, Mary Hanna, April Caravaca, Steven M. Paul

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

Microglia have been shown to contribute to the clearance of brain amyloid β peptides (Aβ), the major component of amyloid plaques, in Alzheimer's disease (AD). However, it is not known whether microglia play a similar role in the clearance of tau, the major component of neurofibrillary tangles (NFTs). We now report that murine microglia rapidly internalize and degrade hyperphosphorylated pathological tau isolated from AD brain tissue in a time-dependent manner in vitro. We further demonstrate that microglia readily degrade human tau species released from AD brain sections and eliminate NFTs from brain sections of P301S tauopathy mice. The anti-tau monoclonal antibody MC1 enhances microglia-mediated tau degradation in an Fc-dependent manner. Our data identify a potential role for microglia in the degradation and clearance of pathological tau species in brain and provide a mechanism explaining the potential therapeutic actions of passively administered anti-tau monoclonal antibodies.

Original languageEnglish
Article number11161
JournalScientific reports
Volume5
DOIs
StatePublished - Jun 9 2015

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