Fig. 4: Analysis of nanoscale colocalization of synaptic proteins and amyloid-beta in Alzheimer’s model mouse brain.

a Example 5-channel and composite maximum intensity projections of a 5xFAD field of view, cropped to show Aβ nanoclusters. (Scale bar, 1 μm). b Bar plots of total volume of select proteins within Aβ nanocluster ROIs (n = 71 ROIs from 9 fields of view from 2 5xFAD animals; Supplementary Table 8 for full statistics, error bars indicate mean ± standard error of the mean). c Bar plots of the fraction of volume of D54D2 occupied by AMPA receptor (error bars are mean ± standard error of the mean, statistical significance determined by Tukey’s multiple comparisons test following one-way ANOVA, p < 0.0001 for all asterisked comparisons except p = 0.0047 for GluA3 vs. GluA4, n = 44 nanocluster ROIs from 8 fields of view from 2 5xFAD animals; Supplementary Table 9(i) for full statistics). d Scatterplot of GluA2 (yellow circles) and GluA4 (blue triangles) volume vs. D54D2 volume within Aβ nanocluster ROIs. Lines indicate the best-fit lines from simple linear regressions, and the shaded regions indicate the 95% confidence interval on the best-fit line (n = 71 ROIs from 9 fields of view from 2 5xFAD animals; Supplementary Table 9(ii) for full statistics). e Scatter plot of GluA2 volume vs. GluA4 volume within Aβ nanocluster ROIs. Black line indicates the best-fit line from a simple linear regression, and the shaded region indicates the 95% confidence interval on the best-fit line (the same n = 71 ROIs from 9 fields of view from 2 5xFAD animals; Supplementary Table 9(iii) for full statistics). f Maximum intensity projections for selected channels of the ROIs circled in black in the plot in c. Scale bar, 50 nm. ****p < 0.0001, ***p < 0.001 **p < 0.01, ns, not significant. WT, wild type. 5xFAD, 5x familial Alzheimer’s disease model mice. The 5xFAD data are from the same animals and fields of view as Fig. 3. Source data are provided as a Source Data file.