Fig. 7. Removing non-lipidated apoE4-Aβ co-aggregates enhances Aβ clearance, reducing secretion of inflammatory markers and cytotoxicity.

A Immunoprecipitation of non-lipidated early-stage co-aggregates from a mixture of non-lipidated and lipidated apoE4-Aβ co-aggregates using the HAE-4 antibody. B Representative two-color TIRF images and sizes of individual apoE4-Aβ co-aggregates before (number of aggregates: 10,277, average size: 0.47 ± 1.95 µm²) and after (number of aggregates: 4354, average size: 0.23 ± 0.39 µm²) immunoprecipitation (data are plotted in log₁₀ scale in inset). C–L Effect of immunoprecipitation on Aβ uptake and cytokine/chemokine release by iMGLs (C–G) and iAstrocytes (H–L). M, N Effect of immunoprecipitation on neurotoxicity of apoE4-Aβ co-aggregates, measured by permeabilization of lipid membranes (M) and LDH release by human neuroblastoma SH-SY5Y cells (N). Data points represent one of three biological replicates (C–L, N) or one of three independent experiments (M); Units of uptake = integrated fluorescence of sample divided by the integrated fluorescence of internalized early-stage Aβ42 aggregates at t₁ for each replicate, as in Fig. 3 (C, H); error bars represent mean values +/− standard deviation of three biological replicates. Statistical significance was calculated using one-way ANOVA with post-hoc Tukey. *P < 0.05, **P < 0.01, ***P < 0.001, ns, non-significant (P ≥ 0.05). Source data are provided as a Source Data file.