Therefore, the common protein, GDNF, involving two distinct cellular events, the 1,25(OH)2D3-VDR pathway and AD-pathological targets, is conducive for positing a mechanistic hypothesis that the protective mechanisms of 1,25(OH)2D3 against Aβ neurotoxicity could be driven by VDR-ligand 1,25(OH)2D3/GDNF interplay that targets the PI3K/AKT/GSK-3β pathway. This evidence concerns the gene GSK3B and Alzheimer disease.