In fact, this adipokine restrains tau phosphorylation, an essential premise for the formation of neurofibrillary tangles and studies in postmortem brains of AD patients showed a dysregulation of intracellular leptin signaling circuitry, with decreased ObRb mRNA levels in brain and colocalization of ObRb protein with neurofibrillary tangles [134], indicating a central resistance in this neurodegenerative disease. This evidence concerns the gene LEP and Alzheimer disease.