Extended Data Fig. 9: The P3 peptide blocks B2M-Aβ coaggregation and neurotoxicity.
a, Immunoblot analysis of Aβ42 oligomer formation. The P3 peptide blocks B2M-induced Aβ42 oligomer formation (This assay was independently repeated seven times; two-sided unpaired Mann Whitney test). b, Co-IP between synthetic Aβ42 and P3 peptides. Similar results were observed in two independent experiments. c, Schematic of the truncated P3 peptides. Three P3-derived subfragments were designed and synthesized based on the P3 β-sheet structure: P3-1 (aa 51–60), P3-2 (aa 61–75) and P3-3 (aa 61–69). d, ThT fluorescence assay for protein aggregation. Truncated P3 peptides were incubated with Aβ42 in the presence of full-length B2M. ThT assays were independently repeated three times, and the data represent the mean values. e, Cell viability of primary neurons treated with the P3 peptide was determined by CCK8 assay. Cultured primary neurons from C57BL/6 mice were incubated with increasing concentrations of P3 or scrambled peptide for 24 hours (n = 5 biologically independent samples per group; two-sided unpaired t-test; Ctrl versus Scrambled peptide or P3 peptide). f, Schematic for the aggregates and peptide injection and Golgi staining assay. g, Schematic for peptide injection and behavioral analysis. h, MWM probe test results (n = 8 mice per group; Platform cross number: two-sided unpaired t-test; Time in quadrant: two-sided unpaired Mann Whitney test). i, Schematic for peptide injection and immunostaining analysis. j, Immunoblot analysis of B2M in the hippocampus of peptide-injected 5×FAD; B2MKI/KI mice (n = 5 mice per group; two-sided unpaired t-test). With the exception of the ThT fluorescence data in (d), the data represent mean ± s.e.m. The P values are indicated on the graphs. For detailed statistical information, see Source Data.
