It is not clear if the general decrease of S1P1 signaling observed in 6-month-old 3xTg-AD mice is a compensatory mechanism to counteract neuroinflammatory events or conversely, is contributing to worsen the pathology, but these evidences point to this neurolipid signaling system as a promising pharmacological target for the treatment of neurodegenerative diseases. Here, S1PR1 is linked to Alzheimer disease.