MAPT and Alzheimer disease: In addition to synaptic degradation and extensive neuronal cell loss, neuropathological characteristics of AD include extracellular senile plaques containing β-amyloid (Aβ) derived from β-amyloid precursor protein (APP) after sequential cleavage by b-secretase and c-secretase, and intracellular neurofibrillary tangles caused by abnormally phosphorylated tau protein (De la Monte and Wands, 2006).