Neuronal activity regulates extracellular tau in vivo

Kaoru Yamada, Jerrah K. Holth, Fan Liao, Floy R. Stewart, Thomas E. Mahan, Hong Jiang, John R. Cirrito, Tirth K. Patel, Katja Hochgräfe, Eva Maria Mandelkow, David M. Holtzman

Research output: Contribution to journalArticlepeer-review

225 Scopus citations

Abstract

Tau is primarily a cytoplasmic protein that stabilizes microtubules. However, it is also found in the extracellular space of the brain at appreciable concentrations. Although its presence there may be relevant to the intercellular spread of tau pathology, the cellular mechanisms regulating tau release into the extracellular space are not well understood. To test this in the context of neuronal networks in vivo, we used in vivo microdialysis. Increasing neuronal activity rapidly increased the steady-state levels of extracellular tau in vivo. Importantly, presynaptic glutamate release is sufficient to drive tau release. Although tau release occurred within hours in response to neuronal activity, the elimination rate of tau from the extracellular compartment and the brain is slow (half-life of ~11 d). The in vivo results provide one mechanism underlying neuronal tau release and may link trans-synaptic spread of tau pathology with synaptic activity itself.

Original languageEnglish
Pages (from-to)387-393
Number of pages7
JournalJournal of Experimental Medicine
Volume211
Issue number3
DOIs
StatePublished - Mar 2014

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