APP and Alzheimer disease: By analogy, the neuronal stress triggered by the many risk factors that favor development of AD, manifested as neuronal overexpression of APP and release of sAPP, may be prime in inducing the dramatic neuroinflammatory responses that then result in a self-amplifying cycle (Figure 1) of increasing neuropathological changes, including neuronal stress, neuroinflammation, and synthesis of the precursors giving rise to formation of the Aβ plaques and neurofibrillary tangles diagnostic of AD.