There is pivotal evidence that tau pathology can be triggered by amyloid-β (Aβ) 
pathology in experimental systems. On the other side, studies on human brain 
specimen have elucidated that tau pathology may occur before amyloid pathology 
is present indicating that in principle tau pathology could also trigger Aβ 
aggregation. To address this question, we have crossed 5XFAD mice coexpressing 
human mutant APP695 with the Swedish, Florida, and London mutations and human 
mutant presenilin-1 (PS1) with the M146L and L286V mutations with the PS19 model 
overexpressing human mutant tau with the P301S mutation. The resulting triple 
transgenic model 5XFAD/PS19 has been characterized at 3 and 9 months of age. A 
dramatic aggravation of hyperphosphorylated tau pathology together with a 
dramatically increased inflammatory response and a loss of synapses and 
hippocampal CA1 neurons in aged 5XFAD/PS19 mice were observed. Extracellular 
amyloid deposits were unaltered. These data support the assumption of tau 
pathology being downstream of amyloid pathology, suggesting that both 
pathologies together trigger the severe neuron loss in the hippocampus in the 
5XFAD/PS19 mouse model.