MAPT and Alzheimer disease: The role of aggregated tau protein during AD goes further: tau accumulation within the neuronal cytoplasm is associated with impaired axonal transport of mitochondria between the cell nucleus and synapse, which leads to severe energy dysfunction and imbalance in the generation of reactive oxygen species (ROS) and nitrogen species (RNS) [12, 13], all together leading to synaptic failure, another classical hallmark of AD and neurodegeneration [14].