Fig. 5.

Delayed TGN-020 treatment impacts its effect on propagating tau pathology. A Study design of delayed treatment experiments. Novel Object Recognition is performed prior to tau infusion, which is then followed either immediately, or 2 or 4 weeks later by chronic TGN-020 treatment. At the end of the study (week 10), the NOR task is repeated, limb clasping is assessed, and the structural MRI of the mouse brain is acquired, prior to culling for immunohistochemistry. Immunohistochemical analysis of tau (AT8) immunoreactivity in the hippocampus, reveals that immunoreactive intensity (B) is reduced with TGN-020 treatment delayed. This results in rescue of novel objective exploration at week 10 (C) and sparing of limb clasping behaviour (D) as a function of the delay in treatment. Structural MRI also reveals alleviation of volumetric differences in regions of significant ipsi > contralateral (e.g. hippocampus (E)) and ipsi < contralateral (e.g. amygdala (F)) difference. ▲=females, ■=males, *=p < 0.05, **=p < 0.01, n = 7–8 per group