GSK3: A possible link between beta amyloid peptide and tau protein

Tau is a neuronal microtubule-associated phosphoprotein that is highly phosphorylated by glycogen synthase kinase 3 (GSK3). Tau phosphorylation by GSK3 regulates tau binding to microtubules, tau degradation and tau aggregation. Tau phosphorylation is important in Alzheimer disease pathology and in other tauopathies. In Alzheimer disease, it has been proposed that the peptide beta amyloid promotes GSK3 activation, resulting in tau phosphorylation. In this work, we review the links between beta amyloid peptide, tau protein and GSK3 that occur in familial Alzheimer disease. We also discuss the possible links between GSK3 and sporadic Alzheimer disease. Finally, we include a brief review of the pathology of animal models overexpressing GSK3.This work was supported by grants from the Comunidad de Madrid (NEURODEGMODELS-CM), the Spanish Comisión Interministerial de Ciencia y Tecnología and the CIBER on Neurodegeneration and by institutional grants from the Fundación Ramón Areces.Peer reviewe