SPHK2 and Alzheimer disease: SphK2 activity declined with increasing Braak stage in both the hippocampus and temporal cortex (Figure 4), and the declining S1P/sphingosine ratio during AD pathogenesis in the temporal GM appears to reflect reduced SphK2 activity, as well as a robust gain of S1P phosphatase activity in the Braak V/VI brains (Figure 5).