MAPT and Alzheimer disease: In addition to the Aβ cascade hypothesis, many other hypotheses have also been proposed to explain the pathologic process of AD, including the tau hypothesis [229], the blood–brain barrier (BBB) dysfunction hypothesis [230], the metal ion dysregulation hypothesis [231, 232], the inflammation hypothesis [233], the oxidative stress and mitochondrial cascade hypothesis [234, 235], and the insulin resistance hypothesis [236].