GHRL and Alzheimer disease: However, the finding that point mutations of the ghrelin gene were associated with the increased propensity to Alzheimer’s disease [237] raised the possibility that deficiency of the ghrelinergic tone can be a causative factor of neurodegeneration, especially in obese subjects who show a paradoxical resistance to ghrelin, which, coupled with leptin and insulin resistance, reflects a decreased resilience of hypothalamic body weight regulation [238].