MAPT and Alzheimer disease: Cdk5 and its neuron-specific activator p35 are required for neurites outgrowth and cortical lamination and the cleavage of p35 to p25 is considered to be one of the reasons for Cdk5 deregulation and hyper activation in AD [147] as the hyperactivated p25/Cdk5 complex both enhances β-secretase (BACE1) activity via phosphorylation [148] and hyper phosphorylates tau [149], thereby disrupting the cytoskeleton and promoting the apoptosis of neurons.