TY - JOUR T1 - Anesthesia-Induced Hyperphosphorylation Detaches 3-Repeat Tau from Microtubules without Affecting Their Stability <em>In Vivo</em> JF - The Journal of Neuroscience JO - J. Neurosci. SP - 12798 LP - 12807 DO - 10.1523/JNEUROSCI.4101-08.2008 VL - 28 IS - 48 AU - Emmanuel Planel AU - Pavan Krishnamurthy AU - Tomohiro Miyasaka AU - Li Liu AU - Mathieu Herman AU - Asok Kumar AU - Alexis Bretteville AU - Helen Y. Figueroa AU - Wai Haung Yu AU - Robert A. Whittington AU - Peter Davies AU - Akihiko Takashima AU - Ralph A. Nixon AU - Karen E. Duff Y1 - 2008/11/26 UR - http://www.jneurosci.org/content/28/48/12798.abstract N2 - In Alzheimer's disease, tau is hyperphosphorylated, which is thought to detach it from microtubules (MTs), induce MT destabilization, and promote aggregation. Using a previously described in vivo model, we investigated whether hyperphosphorylation impacts tau function in wild-type and transgenic mice. We found that after anesthesia-induced hypothermia, MT-free tau was hyperphosphorylated, which impaired its ability to bind MTs and promote MT assembly. MT-bound tau was more resistant to hyperphosphorylation compared with free tau and tau did not dissociate from MTs in wild-type mice. However, 3-repeat tau detached from MT in the transgenic mice. Surprisingly, dissociation of tau from MTs did not lead to overt depolymerization of tubulin, and there was no collapse, or disturbance of axonal MT networks. These results indicate that, in vivo, a subpopulation of tau bound to MTs does not easily dissociate under conditions that extensively phosphorylate tau. Tau remaining on the MTs under these conditions is sufficient to maintain MT network integrity. ER -