APP and Alzheimer disease: In this paper, we used amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice (Jankowsky et al., 2001) (1) to determine the earliest age at which mitochondrial alteration occurs in this mouse AD model; (2) to explore whether neuronal morphological and synaptic dysfunction co-occur with mitochondrial dysfunction; (3) to evaluate whether the earliest defects affect social behavior, which requires normal HIPP-mPFC activity.