Fig. 2

Internalized tau fibrils resist astrocytic degradation mechanisms. (a) Schematic illustration of the experimental design. Human iPSC-derived astrocytes were exposed to human brain-derived tau fibrils extracted from the parietal and temporal lobes of either AD or control brains. Following three days of exposure, astrocytic cultures were washed thoroughly and then maintained for an additional 12 days in tau-free medium. Astrocyte-conditioned medium was collected on day 3 + 4, 3 + 8, and 3 + 12. Astrocytes were fixed on day 3 + 4 and 3 + 12. (b) Confocal imaging confirmed the intracellular localization of Amytracker 680-labeled tau fibrils at day 3 + 4. Scale bar = 10 μm. (c) Representative fluorescence images of tau-burdened astrocytes at day 3 + 4 and 3 + 12. Scale bar = 30 μm. Quantification of cell count (d), average cell area (e), average number of branching points per cell (f) and intracellular Amytracker-680 signal (g) in astrocytes exposed to parietal and temporal tau fibrils. Three AD and two control samples were used. N = 3 culture experiments, n = 10–12 non-overlapping fields per brain sample. The level of significance was set at *p ≤ 0.05, **p ≤ 0.001, ***p ≤ 0.0001, ****p ≤ 0.00001