This demonstrates for the first time a functional relationship between AD-associated human PS1 mutations and dysregulated RyR function in human neurons; this is particularly relevant in light of the central role intracellular calcium signaling plays in synaptic transmission, plasticity, and memory encoding, as well as oxidative stress, apoptosis, and inflammation, [39,43,44]. The gene discussed is PSEN1; the disease is Alzheimer disease.