TAPPing into the potential of inducible tau/APP transgenic mice


Our understanding of the pathological interactions between amyloidosis and tauopathy in Alzheimer’s disease is incomplete. We sought to determine if the relative timing of the amyloidosis and tauopathy is critical for amyloid-enhanced tauopathy.


We crossed an inducible tauopathy model with two ?-amyloid models utilizing the doxycycline-repressible transgenic system to modulate timing and duration of human tau expression in the context of amyloidosis, and then assessed tauopathy, amyloidosis, and gliosis.


We combined inducible rTg4510 tau with APPswe/PS1dE9 [Line 85 (L85)] mice to examine the interactions between A? and tauopathy at different stages of amyloidosis. When we initially suppressed mutant human tau expression for 14-15 months and subsequently induced tau expression for 6 months, severe amyloidosis with robust tauopathy resulted in rTg4510/L85 but not rTg4510 mice. When we suppressed mutant tau for 7 months before inducing expression for a subsequent 6 months in another cohort of rTg4510/L85 and rTg4510 mice, only rTg4510/L85 mice displayed robust tauopathy. Lastly, we crossed rTg4510 mice to tet-regulated APPswe/ind [Line 107 (L107)] mice, using doxycycline to initially suppress both transgenes for 1 month before inducing expression for 5 months to model early amyloidosis. In contrast to rTg4510, rTg4510/L107 mice rapidly developed amyloidosis, accompanied by robust tauopathy.


These data suggest that tau misfolding is exacerbated by both newly forming A? deposits in younger brain and mature deposits in older brains. Refined use and repurposing of these models provide new tools to explore the intersection of aging, amyloid and tauopathy, and to test interventions to disrupt the amyloid cascade.