APP and Alzheimer disease: Steve Barger’s discovery of a role for a secreted fragment of APP, sAPP, in synthesis and release of the pro-neuroinflammatory cytokine IL-1 [20], together with studies demonstrating the importance of IL-1 in promotion of neurodegenerative events [32], underscores the importance of APP, over and above its importance as the precursor of the Aβ in the senile plaques characteristic of AD and DS.