Fig. 7

AD fibril-exposed astrocytes induce synaptic and metabolic impairment in human neurons. (a) Schematic illustration of the experimental design. Human iPSC-derived astrocytes were exposed to brain-derived tau fibrils. Subsequently, human iPSC-derived neurons were treated with astrocyte-conditioned medium (ACM) for 14 days. (b) Representative fluorescence images of synaptophysin and βIII-Tubulin staining of neurons at day 3 + 14. Scale bar = 50 μm. (c) Quantification of synaptophysin-positive puncta normalized to cell area (measured using βIII-Tubulin signal) at day 3 + 14 (N = 3 culture experiments, n = 10–12 non-overlapping fields per brain sample). (d) Measurement of ATP levels in neurons at day 3 + 14 (N = 4 culture experiments, n = 1 measurement per brain sample). Both for the synaptophysin and ATP analyses, three AD and two control parietal samples were used. Each violin plot in (c) represents a total of 12 images per sample. Bars in (d) represent the mean and SD of measurements from four separate neuronal cultures per brain sample. The level of significance was set at *p ≤ 0.05, **p ≤ 0.001, ***p ≤ 0.0001, ****p ≤ 0.0000