Figure 6. Stabilized E-S complexes trigger synaptic loss in C. elegans.

(A) Lifespan analysis of double-transgenic line C99 V50F/M51F + PSEN1 compared with C99 + PSEN1, C99 I45F + PSEN1, and C99 V44F/I45F + PSEN1 lines.

(B) Quantification of dorsal and ventral synaptic puncta in these transgenic lines. Two-way ANOVA for all possible pairs using Tukey’s post hoc test; *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p < 0.0001. Statistical differences are shown only for the earliest day on which significance was seen between a given line and C99 + PSEN1.

(C) Sections (100 μm) of representative confocal microscopic images of dorsal and ventral synaptic puncta in these transgenic lines. The same data used in Figure 4 for C99 + PSEN1, C99 I45F + PSEN1, and C99 V44F/I45F + PSEN1 were reproduced in (B)–(D) for direct comparison with C99 V50F/M51F + PSEN1.

(D) Lifespan analysis of double-transgenic line C99 + PSEN1 L166P and single-transgenic line PS1 L166P compared with C99 + PSEN1.

(E) Quantification of dorsal and ventral synapses in double-transgenic lines C99 + PSEN1 and C99 + PSEN1 L166P. Note: PS-1 L166P monogenic lines were sensitive to the anesthetic agent phenoxy propanol, leading to dying on agarose pads during sample preparation for imaging. Thus, confocal imaging of these animals was not possible. Two-way ANOVA for all possible pairs using Tukey’s post hoc test; *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001, ****p < 0.0001. Statistical differences are shown only for days on which significance was seen within a given line.

(F) Sections (100 μm) of representative fluorescence microscopic images of dorsal and ventral synaptic puncta in these transgenic lines. The same data used in Figure 4 for C99 + PSEN1 were reproduced in (D)–(F) for direct comparison with C99 + PSEN1 L166P and PSEN1 L166P (lifespan) or with only C99 + PSEN1 L166P (synaptic puncta). All experiments shown were repeated with independent transgenic lines, giving similar results.