They can directly affect mitochondria from the surface interacting with components of mitochondrial protein import machinery;2, 3, 4, 5 in other cases, they interact with components of respiratory chain complexes, mitochondria permeability transition pore or redox enzymes.6, 7, 8, 9, 10 In AD, both APP and Aβ directly associate with mitochondria causing their dysfunction. The gene discussed is APP; the disease is Alzheimer disease.