Theimportance of GSK-3 in the pathogenesis of AD has been emphasised by reports that aGSK3B polymorphism is a significant risk factorfor the development of LOAD [273].Both isoforms of GSK-3 (GSK-3β and GSK-3α) appear to induce the hyperphosphorylationof tau [274, 275], but GSK-3α alone regulates the cleavage ofAPP and would appear to exert this role in the very early phase of the disease[276–278]. The gene discussed is MAPT; the disease is Alzheimer disease.