RYR2 and Alzheimer disease: The alteration of RyR expression in AD-affected brains was first described in 1999 by Kelliher et al.[107], who showed that [3H] ryanodine binding (indicative of RyR expression protein) is elevated in hippocampal regions (subiculum, CA2 and CA1) of human post-mortem tissue at early stages of the disease, i.e. prior to extensive neurodegeneration and overt Aβ plaque deposition[107].