APP and Cognitive impairment: The 3xTg-AD mice carry AD-related mutation including human PS1 M146V, human APP Swedish, and human tau P301L [182], and develop Aβ plaques and neurofibrillary tangle-like pathologies in a progressive and age-dependent manner, starting at ~9 and ~12 months respectively but show cognitive impairment as early as 3–5 months of age [182–185].