Specifically, we show that sub-chronic dantrolene treatment (4 weeks) normalizes many of the core pathogenic features observed in presymptomatic 3xTg-AD and adult TASTPM mouse models, including dysregulated ER Ca2+ signaling, Aβ deposition, increased RyR2 expression levels, and synaptic transmission and plasticity abnormalities, while having little effect in NonTg controls. The gene discussed is RYR2; the disease is Alzheimer disease.