Potential substrates and mediators of early life experiences that may influence the development of AD pathology and cognitive decline are: programming of the hypothalamic–pituitary–adrenal axis, priming of the neuroinflammatory response, dendritic and synaptic complexity and function, overall brain plasticity, and proteins such as early growth response protein 1 (EGR1), activity regulated cytoskeleton-associated protein (Arc), and repressor element-1 silencing transcription factor (REST). The gene discussed is ARC; the disease is Alzheimer disease.