A recent publication in Neurodegenerative diseases ties Alzheimer's-associated synapse loss to perturbed calcium regulation in dendritic spines. The researchers found that both mice expressing an Alzheimer's disease (AD) gene and also human brains with sporadic AD displayed less calcium sensor STIM2 and that overexpressing SIM2 rescues spine deficiency. This observation has lead researchers to question whether this may be the common mechanism for memory loss-associated spine loss in both AD and aging. How does less calcium entering spines destabilize mature synapses?