Since the use of drugs targeting S1P signaling such as fingolimod (Gilenya®, Novartis Pharma AG, Basel, Switzerland), which induces a functional antagonism of S1P1 receptors (i.e., reducing S1P1-mediated signaling), was approved as immunotherapeutic drug for the treatment of multiple sclerosis, further studies in AD models will contribute to explore the potential of S1P1 agonists also for AD treatment. This evidence concerns the gene S1PR1 and Alzheimer disease.