PSEN1 and Alzheimer disease: Other very aggressive models, such as the 5xfAD mice harboring 5 human transgenes (3 copies of human APP with the Swedish (K670N, M671L), Florida (I716V), and London (V717I) mutations and two copies of human PSEN1 with M146L and L286V mutations), display many pathological AD hallmarks, such as amyloid plagues, synaptic degeneration, and microglia activation.