To identify molecular pathological alterations in Alzheimer’s disease (AD) brains, we performed interspecies comparative microarray analyses using RNA prepared from postmortem human brain tissues donated for the Hisayama study, and hippocampal RNAs from the triple-transgenic mouse model of AD (3xTg-AD). We found altered expression of genes involved in insulin production, insulin signaling and mitochondrial function in AD brains. Mitochondrial dysfunction is considered to have a pivotal role for developing AD, we further examined effects of human mitochondrial transcriptional factor A (hTFAM) transgene, which plays important roles to maintain mitochondrial homeostasis, on the pathology of 3xTg-AD mice.