Up-regulation of SGPL1 and reduced expression of SPHK1, with a subsequent decrease in S1P, has been associated with neurodegeneration in Alzheimer’s disease (He et al., 2010; Ceccom et al., 2014; Couttas et al., 2014) and has also been described in animal models of Huntington’s disease (HD) as well as in post-mortem brain tissues from patients with HD (Di Pardo et al., 2017). This evidence concerns the gene SGPL1 and early-onset autosomal dominant Alzheimer disease.