APOE and Alzheimer disease: First, the AD model used reflects familial (early-onset) AD, whereas APOE4 is a genetic risk factor for sporadic late-onset AD and most studies reporting a link between sphingolipid levels and cognitive decline were performed in patients with sporadic late-onset AD (Mielke et al., 2010a, 2011; Mielke and Haughey, 2012).