APP and Cognitive impairment: The 3xTg-AD-H mice exhibit mainly intracellular Aβ accumulation before 12 months of age, accompanied by increased levels of intracellular APP sub-products, as well as Tau pathologies such as intracellular NFT and cognitive impairment, accompanied by astrocytosis but not microgliosis (Supplementary Figs S8, S9 and S10)9,17,34,35.