MAPT and Alzheimer disease: Major pathological hallmarks of AD are the deposition of aggregated amyloid β-protein (Aβ) contributing to the formation of extracellular amyloid plaques (senile plaques) and the intra-neuronal accumulation of hyper-phosphorylated tau protein, which, over time, lead to synaptic dysfunction, neuronal loss and neuroinflammation (Hardy and Selkoe, 2002[21]; Reitz and Mayeux, 2014[42]).