Activation of glycogen synthase kinase-3 beta mediates β-amyloid induced neuritic damage in Alzheimer's disease

► Abeta activates GSK3beta in cultured neurons, APP-tau mice and AD brains. ► Abeta exposure alters neurite morphology and inhibits CREB-target gene expression. ► Blocking either Abeta or GSK3beta is each sufficient to prevent this phenotype. ► Introduction of an uninhibitable GSK3beta produces a phenocopy in absence of Abeta. ► GSK3 inhibition rescues neurite changes, CREB inhibition and cognition in vivo.