MAPT and Alzheimer disease: Taken together, calcium dysregulation contributes to AD progression through multiple mechanisms: (i) the disturbance of calcium homeostasis may cause damage to neuronal structures, leading to cell necrosis and dysfunction; (ii) increased intracellular calcium promotes Aβ deposition; (iii) calcium overload causes abnormal tau phosphorylation and inhibits its binding to microtubules, resulting in neurofibrillary tangle formation; and (iv) disruption of calcium homeostasis leads to abnormal synaptic plasticity, contributing to cognitive impairment in AD patients [44].