Updated project metadata. Transgenic mouse models have been widely used to investigate the pathology of Alzheimer’s disease (AD). To elucidate underlying mechanisms of AD pathogenesis by amyloid beta (Aβ) and tau, we have generated a novel animal model of AD; ADLP - APT mice (Alzheimer’s Disease-Like Pathology) – carrying mutations of human amyloid precursor protein (APP), human presenilin-1 (PS1) and human tau. We profiled 9,824 proteins in the hippocampus of ADLP model mice using quantitative proteomics. To identify functional signatures in pathology of ADLP - APT mice, in-depth bioinformatics analysis was performed. For a longitudinal change of differentially expressed proteins (DEPs), we identified ADLP - APT mice hippocampal proteome in an age-dependent manner. Network maps of interactome between Aβ and tau in newly generated ADLP - APT mice reveal relationship between accelerated NFT pathology of AD and proteomic changes.