Figure 4.

Astrocytes derived from fAD differently degrade monomeric and aggregated tau in vitro. (a) Bioimaging revealed the presence of monomeric and aggregated tau in the lysosomal compartment in all clones. Scale bar: 20 µm. (b) Graph showing percentage of viable astrocytes from NDC, sAD and fAD after exposure to monomeric or aggregated tau at 24 and 48 h. Bio-imaging of tau uptake by (c) NDC, (d) sAD and (e) fAD astrocytes 24 h after incubation with Alexa 546-conjugated monomeric tau. Representative live cell images of (f) NDC, (g) sAD and (h) fAD astrocytes at 48 h after removal of media containing monomeric tau (at 24 h). Graph showing mean fluorescence intensity of tau within the astrocytes at (i) 24 h and (j) 48 h, respectively. Bio-imaging of tau uptake by (k) NDC, (l) sAD and (m) fAD astrocytes 24 h after incubation with Alexa 546-conjugated aggregated tau. Representative live cell images of (n) NDC, (o) sAD and (p) fAD astrocytes at 48 h after removal of media containing aggregated tau (at 24 h). Note the drastic decrease in fluorescence intensity in the NDC and sAD astrocytes, and the accumulation of AggTau in astrocytes from fAD iPSCs at 48 h. Graph showing fluorescent intensity/cell of aggregated tau uptake at 24 h (q), and levels of aggregated tau at 48 h (r). One-way ANOVA followed by Tukey’s multiple comparisons tests was used for statistical analysis, (n = 3/group; n = 3 experimental repeats). *** p < 0.0001. Scale bar: 50 nm; inset: 20 nm.