GSK3β then phosphorylates on the serine residue of the SRXXS region in the microtubule-binding domain (MTBD) of MACF1, resulting in a dissociation of MACF1 from microtubules, an alteration in cytoskeletal networks—and hence, the structure and function of synapses—and a reduction in plasticity, the loss of recognition, and finally AD. Here, MACF1 is linked to Alzheimer disease.