S1PR1 and Alzheimer disease: Fingolimod-induced activation of microglial S1PRs (sphingosine-1-phosphate receptors) was shown to interfere with microglia activation in the cortex of 5xFAD mice [24], to inhibit neuronal Aβ production [32], to decrease Aβ42 and Aβ40 levels in the brain of AD mouse models [24,33], to regulate Aβ traffic across the BBB [34], and to promote the conversion of proinflammatory M1 microglia to the anti-inflammatory M2 state [35].