MAPT and Alzheimer disease: Intracellular copper ions can affect the hyperphosphorylation of tau proteins through a variety of mechanisms, including altering the conformation of tau proteins and activating kinases (e.g., GSK3β), which in turn leads to the formation of neurofibrillary tangles, altogether disrupting intracellular signaling pathways and exacerbating the pathological process in AD patients.