In addition to promoting Aβ overproduction by activating β- and γ-secretases and/or inhibiting α-secretase, oxidative stress can cause tau hyperphosphorylation by activating protein kinases (e.g., GSK-3β, cyclin-dependent kinase 5 (CDK5), MAPK, etc.)and/or inhibiting Protein Phosphatase 2A (PP2A) [192], suggesting one of the root causes of AD, supporting the metal ions hypothesis. This evidence concerns the gene MAPT and Alzheimer disease.