The present study used a newly developed preclinical AD mouse model (APPKI) to explore for the first time the mitochondrial bioenergetics and dysfunction caused by Aβ-related pathology, including (1) decreased ATP production, increased mitochondrial membrane potential, and ROS production and (2) downregulation of MFN2 protein level at the early stage of diseases parallel with cognitive deficit. The gene discussed is MFN2; the disease is Cognitive impairment.