SPHK2 and Alzheimer disease: While the overall SphK2 protein levels were decreased in the brains of individuals suffering from dementia, which was explained by progressive neuronal loss and the predominantly neuronal expression of SphK2 in the brain (Blondeau et al., 2007) the relative in vitro activitiy of SphK2 normalized to SphK2 protein levels was significantly increased in AD brains (Takasugi et al., 2011).