Fig. 4.

Reduced axonal PIP₂ accounts for oligomeric Aβ-induced suppression of presynaptic release probability at the SC-CA1 synapse. a Confocal images of primary hippocampal neurons showing colocalization of PIP₂, MAP2, and neurofilament (NF) along neuronal processes in control, DMSO-treated, and oligomeric Aβ-treated hippocampal neurons. Bar, 50 μm. b Histograms showing oligomeric Aβ suppresses PIP₂ levels significantly in both dendrites (MAP2⁺, NF⁺, upper panel) and axons (MAP2⁻, NF⁺, bottom panel). One-way ANOVA with post hoc Dunnett’s test; F_(2,55) = 4.95 (upper); F_(2,55) = 9.39 (bottom); *P < 0.05; **P < 0.01; ***P < 0.001; N = 19–20 per group. c Quantification of PIP₂ levels measured with ELISA showing oligomeric Aβ suppresses PIP₂ in cultured hippocampal neurons. One-way ANOVA with post hoc Dunnett’s test; F_(2,15) = 5.87; *P < 0.05; N = 6 per group. d Representative traces of mEACs recorded from isolated hippocampal neurons (an example shown in inset at bottom) in vehicle-treated medium (Veh), oligomeric Aβ-supplemented medium (Aβ), oligomeric Aβ-supplemented medium with intracellular application of PIP₂ (Aβ + PIP₂), or vehicle-treated medium with intracellular application of PIP₂ (PIP₂). Bar, 50 μm. e, f Cumulative plots (e) and mean values (f) of mEAC amplitude (left) and frequency (right) in isolated hippocampal neurons in various conditions. Kolmogorov-Smirnov test in e; one-way ANOVA with post hoc Dunnett’s test in f, F_(3,16) =0.54 (amplitude); F_(3,16) =5.47 (frequency); *P < 0.05; **P < 0.01; ***P < 0.001; N = 4–6 per group. Data are mean ± SEM. Source data are provided as a Source Data file