APP and Alzheimer disease: Of note, downregulation of RyR2 expression in human AD brain postmortem samples occurs very early in the progression of this disease (Kelliher et al., 1999), and abnormalities in RyR2 function have been reported in SH-SY5Y neuroblastoma cells expressing APP harboring the double Swedish mutations (Bussiere et al., 2017) and in rodent transgenic AD models (Lacampagne et al., 2017).