Figure 6.

VHH Z70 reduces human Tau seeding activity induced by h-AD brain-derived material in THY-tau30 Tg mouse model

(A) Bilateral intra-cranial injection of LVs to express either VHH anti-GFP or VHH Z70 was performed in 1-month-old THY-tau30 mice. Induction of the tauopathy occurred by a second bilateral injection, at the same coordinates, 15 days after with human h-AD. Mice were killed and perfused 1 month later (aged 2.5 months). (B) The whole brain was processed for immunohistochemical analysis using AT8 for the control group (labeled VHH anti-GFP + AD; n = 9) corresponding to injection of LVs VHH anti-GFP followed by h-AD injection and the group (labeled VHH Z70 + AD; n = 7) corresponding to LVs VHH Z70 followed by h-AD injection. Enlarged images are taken from the hippocampus (injection site, AP: −2.46). Scale bars are indicated on the figure. (C) Each data point corresponds to the quantification for one hemisphere. Results are presented as AT8 immunoreactivity (immunoreactive area normalized to the whole area). ∗p value <0.05. Error bars: SD. (D) In a region of the hippocampus (molecular layer) with strong induction of the pathology (detected using AT-8 antibodies, visualized in red, see VHH anti-GFP + AD) and good diffusion of LVs expressing Z70 (detected using mCherry antibodies, visualized in green, see VHH Z70 + AD), there is almost no Tau pathology (red labeling) in neurons positive for VHH-Z70 expression (green labeling). Immunohistochemical analysis is shown for two animals (VHH Z70 + AD) with different levels of pathology. Larger views of the analysis are shown in Figure S16.