Tau-knockout mice show reduced GSK3-induced hippocampal degeneration and learning deficits.

Journal Article (Journal Article)

It has been proposed that deregulation of neuronal glycogen synthase kinase 3 (GSK3) activity may be a key feature in Alzheimer disease pathogenesis. We have previously generated transgenic mice that overexpress GSK3beta in forebrain regions including dentate gyrus (DG), a region involved in learning and memory acquisition. We have found that GSK3 overexpression results in DG degeneration. To test whether tau protein modified by GSK3 plays a role in that neurodegeneration, we have brought GSK3 overexpressing mice to a tau knockout background. Our results indicate that the toxic effect of GSK3 overexpression is milder and slower in the absence of tau. Thus, we suggest that the hyperphosphorylated tau mediates, at least in part, the pathology observed in the brain of GSK3 overexpressing mice.

Full Text

Duke Authors

Cited Authors

  • Gómez de Barreda, E; Pérez, M; Gómez Ramos, P; de Cristobal, J; Martín-Maestro, P; Morán, A; Dawson, HN; Vitek, MP; Lucas, JJ; Hernández, F; Avila, J

Published Date

  • March 2010

Published In

Volume / Issue

  • 37 / 3

Start / End Page

  • 622 - 629

PubMed ID

  • 20004245

Electronic International Standard Serial Number (EISSN)

  • 1095-953X

Digital Object Identifier (DOI)

  • 10.1016/j.nbd.2009.11.017


  • eng

Conference Location

  • United States