Increased Dickkopf‐1 expression in transgenic mouse models of neurodegenerative disease

• DOI: 10.1111/j.1471-4159.2009.06566.x
• Publication Date: 2009-12-29T13:52:16Z
• Authors: Maria Cristina Rosi; Ilaria Luccarini; Cristina Grossi; Anna Fiorentini; Maria Grazia Spil...; Antonella Prisco; Carla Scali; Marco Gianfriddo; Andrea Caricasole; Georg C. Terstappen; Fiorella Casamenti
• Keywords: GSK3B; Tauopathy

To investigate the role of Wnt inhibitor Dickkopf-1 (DKK-1) in pathophysiology neurodegenerative diseases, we analysed DKK-1 expression and localization transgenic mouse models expressing familial Alzheimer's disease mutations a frontotemporal dementia mutation. A significant increase was found diseased brain areas all lines, where it co-localized with hyperphosphorylated tau-bearing neurons. In TgCRND8 mice, immunoreactivity detected neurons surrounding amyloid deposits within choline acetyltransferase-positive basal forebrain. Active glycogen synthase kinase-3 (GSK-3) to co-localize phospho-tau staining. Downstream GSK-3, reduction beta-catenin translocation nucleus, indicative impaired signaling functions, as well. Cumulatively, our findings indicate that is associated events lead neuronal death diseases support for key mediator neurodegeneration therapeutic potential.