PAR-2 receptors are located on keratinocytes and sensory nerves, and researchers have argued that the stimulation of PAR-2 is a major pathway for non-histaminergic pruritus in AD and the induction of neurogenic inflammation, resulting in the release of neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) (23). This evidence concerns the gene F2RL1 and Alzheimer disease.