LEP and Alzheimer disease: Leptin, an adipokine increase in obesity, has a role in the hypothalamus, CNS nuclei such as the cerebral cortex and hippocampus. These regions are the first to be affected by chronic neurocognitive deficits containing the long-acting leptin receptor, a unique receptor capable of completing leptin signaling. Leptin resistance due to obesity is an important risk factor for AD. Obesity is a chronic low-grade inflammatory state responsible for leptin resistance through various mediators.