Tau Protein Mediates APP Intracellular Domain (AICD)-Induced Alzheimer’s-Like Pathological Features in Mice
Fig 9
Tau mediates AICD-induced AD-like phenotypes.
(A, B) AICD activates GSK-3β; this in turn phosphorylates tau, which accumulates in somato-dendritic compartments. Increased somato-dendritic tau results in a number of AD-like features in AICD animals, including phosphorylation of NMDA receptors (NMDAR), which leads to increased susceptibility to excitotoxicity. (C) Increasing the amount of tau by transgenic overexpression of human tau (h-Tau) resulted in increased somato-dendritic tau and elevated phosphorylation of NMDAR. Increased NMDAR phosphorylation led to increased susceptibility to excitotoxic effects and aggravated AD-like pathologies. (D) Loss of tau prevented increased NMDAR-phosphorylation, resulting in normalization/lowering of hyper-excitability, finally reducing/ameliorating several key AD-like features in AICD mice.