Neuronal Activity regulates extracellular tau in vivo

Kaoru Yamada, Jarrah Holth, Fan Liao, Floy Stewart, Thomas Mahan, Hong Jiang, John Cirrito, Tirth Patel, Katja Hochgrafe, Eva-Maria Madelkow, David Holtzman; 2014 JEM 211(3) pp 387-393 Read More


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.

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Posted on April 10, 2014
Posted in: HPAN, Neurodegeneration, Neurovascular Injury & Repair, Publications Authors: ,