Fig. 1

APP Iberian negatively impacts presynaptic differentiation. A The schematic representation shows APP WT and the APP FAD mutants which are analyzed. The FAD mutations were introduced into N-terminally c-myc-tagged APP695. The substituted amino acids are highlighted. The Aβ sequence is marked in blue and the transmembrane region in light grey (not to scale). Secretase cleavage sites are indicated by arrows. Numbers underneath the amino acids refer to their positions within the Aβ sequence. B HEK293T cells expressing c-myc-tagged APP WT, Swedish, Flemish, Arctic, Iowa, Iberian, neuroligin1 (positive control) or GFP (negative control) were seeded on WT primary cortical neurons (DIV7) and analyzed 24 h later via immunocytochemistry using anti-c-myc, anti-MAP2 (dendritic marker), and anti-synaptophysin (marker for presynaptic vesicles) antibodies. Scale bar, 10 µm. C Quantification of synaptophysin-positive puncta per HEK293T cell. D Quantification of synaptophysin-covered area per HEK293T cell. Bars represent mean values ± SEM of four independent experiments, n > 16/N = 4; Kruskal–Wallis test followed by Dunn’s multiple-comparison test; the * symbol represents significant differences in comparison with APP WT. *p < 0.05, **p < 0.01, and ***p < 0.005