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. 2018 Aug 23;35:270–278. doi: 10.1016/j.ebiom.2018.08.041

Fig. 1.

Fig. 1

Two-photon in vivo live imaging reveals that tau mAbs cross the blood-brain-barrier and are primarily detected within neurons. Neuronal 4E6 is cleared faster than 6B2 in htau/PS1 mice and neuronal 6B2 is cleared more slowly in htau/PS1 mice than in WT mice.

AAV5-hSyn-eGFP was used to specifically label neurons with GFP in WT or htau/PS1 mice. Alexa 568-IgG1/6B2/4E6 (100 μg) was injected into the femoral vein. Serial two-photon images were then collected from the same brain region over 14 days. a. Representative two-photon image of tau mAb 6B2 brain signal in live htau/PS1 mice. Neuronal (green) intensity remained constant over time, whereas 6B2 (red) intensity decreased during the same period. b. The percentage of 6B2 within neurons remained constant over time although the signal decreased (see a and c). R is Pearson's correlation coefficient for pixels where both 6B2 and neuron channels are above their respective threshold within 6B2-positive neurons. c. Quantitative analysis of antibody neuronal signals during the 14 day imaging period in htau/PS1 mice. F (3, 35) = 117.8, p < .0001 for time factor and F (2, 35) = 25.68, p < .0001 for group factor. 6B2 was cleared more slowly from the neurons on Day 4, Day 7 and Day 14 (p = .0047, .0004 and .0129, respectively, compared to IgG1 on the same days, two-way ANOVA repeated measures, followed by Tukey's multiple comparisons test). d. Quantitative analysis of neuronal antibody signals during the 7 day imaging period in WT mice, showing for comparison neuronal signals in htau/PS1 mice. F [2, 24] = 217.2, p < .0001 for time factor and F [3, 12] = 15.11, p = .0002 for group factor. At 7 days post-injection, 6B2 neuronal signal had decreased to 23% in WT vs. 71% in htau/PS1 mice, compared to Day 1. The 6B2 neuronal signal differed significantly in these two groups on Day 4 (p = .0342) and Day 7 (p = .0196; Tukey's post-hoc test). Scale bar = 10 μm. F/F0: Ratio of average fluorescence intensity on Day 1 vs. other days. All data are presented as mean ± SEM.*: p < .05; **: p < .01; ***: p < .001.