Fig. 9

5xFAD and human AD patient serum-derived exosomes trigger apoptosis in cells induced by interaction between mitochondrial VDAC1 and Aβ. Representative immunofluorescence images of N2a cells incubated with (a) AD patient exosomes or (b) 5xFAD mouse serum-derived exosomes. FLICA assays were followed by PLAs for VDAC1-Aβ complex formation. Images show that cells with VDAC1-Aβ complexes undergo apoptosis (arrows). c Primary cultured neurons incubated with 5xFAD serum exosomes followed by FLICA assays and PLAs. Arrows indicate neurons colabeled for VDAC1-Aβ complexes and caspase 3 activation. These cells show pyknic nuclei (condensed DAPI labeling) indicative of apoptois. d Western blot with N2a cell lysate immunolabeled for cleaved caspase 3 using GAPDH as a reference protein. Blot is representative of three independent experiments. e Relative fold expression of cleaved caspase 3 normalized to GAPDH. One-way ANOVA followed by Tukey correction. N = 3. **p < 0.001