Figure 4.

Application of amyloid-beta(1-42) altered BDNF transport with faster onset than observed for other Aβ peptides. Dissociated hippocampal neurons derived from 5xFAD wild-type littermates were transfected at 10 DIV with fluorescently labeled BDNF. The dynamic behavior of BDNF-containing vesicles was analyzed by live cell imaging after (a) acute and long-term (b) treatment with different amyloid-beta peptides. (a) Acute treatment with amyloid-beta(1-42) influenced average speed of retrogradely directed BDNF-containing vesicles. Bar diagrams show the mean values of the indicated motional properties after acute treatment with different amyloid-beta peptides. The average speed during motion was significantly reduced in neurons treated with amyloid-beta(1-42) compared to neurons treated with solvent (0,1% DMSO), amyloid-beta(3-42), or amyloid-beta(3(pE)-42), respectively (^∗ p < 0.05, ^∗∗ p < 0.01, one-way ANOVA followed by post hoc Tukey Test). (b) Long-term treatment with amyloid-beta (24 h) influenced different motional properties of BDNF transport. (left) Bar diagram shows the percentage of immobile BDNF-containing vesicles in hippocampal neurons after treatment with different amyloid-beta peptides. (right) Table shows the mean values for the different motional properties of anterogradely and retrogradely directed BDNF-containing vesicles in hippocampal neurons. Note that all motional properties were significantly changed after 24 h treatment with amyloid-beta(1-42) compared to control conditions. Long-term incubation with amyloid-beta(3-42) or amyloid-beta(3(pE)-42) also significantly influenced some motional properties of BDNF-containing vesicles (^∗ p < 0.05, ^∗∗ p < 0.01, ^∗∗∗ p < 0.001; one-way ANOVA followed by post hoc Tukey's test). Error bars represent SEM.