MAPT and Alzheimer disease: Senile plaques formed by extracellular Aβ aggregates and neurofibrillary tangles due to tau protein hyperphosphorylation were prevalent in the brains of AD patients and were considered to be the main pathological markers of AD development, and their synthesis and metabolism were regulated by multifactorial factors in the brain, in particular estrogen (Genazzani et al., 2007).