This downward spiral is further exacerbated by the fact that reduced canonical Wnt signalling strength, as brought about by Dkk1 and Aβ treatment or in transgenic mice expressing constitutively active Gsk3b (S9A), was shown to decrease MDR1 (P-gp) expression in brain endothelial cells in vitro and in vivo as well as in the hippocampus of AD patients [246,251,252,253]. This evidence concerns the gene GSK3B and Alzheimer disease.