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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

Open Access Publications

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 …