While this poses some questions about how good the models are at studying the risk of AD, we can assume that in a mouse model without overexpression of human APP, different protein–protein interactions, receptor-ligand interactions, and downstream intracellular and extracellular effects, replicate true physiological or pathophysiological conditions responsive to regulatory mechanisms at various stages of a neurodegenerative disorder, including AD. The gene discussed is APP; the disease is Alzheimer disease.