It was a simple extension of this observation to look at Alzheimer’s disease (AD) using several murine models of familial AD and show that leaky RyR2 channels upstream of amyloid and neurofibrillary tangles could be rescued either pharmacologically (with a Rycal) or genetically by crossing of the mice with RyR2-S2808A mice (27, 28). The gene discussed is RYR2; the disease is early-onset autosomal dominant Alzheimer disease.