MAPT and Alzheimer disease: In AD, the accumulation of β-amyloid (Aβ) leads to the formation of neuritic plaques outside nerve cells and neurofibrillary tangles inside nerve cells by hyperphosphorylated tau protein, disrupting physiological functions and resulting in synaptic dysfunction, neuronal loss, and microglial activation64; concomitantly, BDNF level was decreased in AD patients65,66.