Fig. 6

IAPP-tau PFFs induce cognitive impairment and synaptic dysfunction in vivo. Three-month-old male mice were injected with PBS, tau PFFs or IAPP-tau PFFs, respectively. The mice were sacrificed three months after PFF injection. a Spatial memory was assessed by the Morris water maze test. Shown are the distance traveled to the platform by mice injected with PBS, Tau PFFs, or IAPP-Tau PFFs. b Integrated time traveled in Morris water maze test. AUC, area under the curve. c Average swim speed of mice in three groups. d Probe trial results. n = 9 mice in PBS group, n = 12 mice in Tau PFFs group, n = 7 mice in IAPP-tau PFFs group. e Time spent in the novel arm in the Y-maze test. n = 7 mice per group. f Long-term potentiation (LTP) of fEPSPs was induced by 3 × TBS (4 pulses at 100 Hz, repeated three times with a 200-ms interval). The magnitude of LTP and synaptic transmission was assessed by input/output (I/O). g Representative fEPSPs of hippocampal slices prepared from mice in three groups. n = 3 mice per group. h Electron microscopy of synapses (top) and magnification (below). Scale bar, 1 μm in the top panel, 200 nm in the lower panel. i The number of synaptic clefts. j Postsynaptic density. k Length of the active zone. l Width of synaptic clefts. n = 10–15 slices per group. m, n Golgi staining of dendritic spines of hippocampal slides. Scale bar, 20 μm. n = 10 slices per group. o Western blot analysis of synaptic markers in the ipsilateral hippocampus of tau P301S mice. p-r Quantification for synaptophysin (p), synapsin I (q), and PSD95 (r), n = 3 mice per group. Data are presented as means ± SEM. One-way ANOVA followed by Tukey’s post hoc test. *P < 0.05, **P < 0.01, ***P < 0.001. n.s. not significant