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Philos Trans R Soc Lond B Biol Sci. 2013 Dec 2;369(1633):20130144. doi: 10.1098/rstb.2013.0144. Print 2014 Jan 5.

Microtubule-associated protein tau is essential for long-term depression in the hippocampus.

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Department of Aging Neurobiology, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, , 35 Gengo, Morioka, Obu, Aichi 474-8522, Japan.


The microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is believed to have a synaptic origin. To investigate a possible synaptic function of tau, we studied synaptic plasticity in the hippocampus and found a selective deficit in long-term depression (LTD) in tau knockout mice in vivo and in vitro, an effect that was replicated by RNAi knockdown of tau in vitro. We found that the induction of LTD is associated with the glycogen synthase kinase-3-mediated phosphorylation of tau. These observations demonstrate that tau has a critical physiological function in LTD.


Alzheimer's disease; hippocampus; long-term depression; synaptic plasticity; tau

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