Fig. 5
Lower Aβ-uptake of APOEε4( +)- derived M1- and M2- macrophages. a, b Schematic overview of TREM2 proteolytic cleavage product sTREM2 formation and TREM2-modulated Aβ uptake. c Confocal microscopy analysis of fluorescence Aβ (green)-uptake by long-term differentiated M1- and M2- macrophages in FCS at 24 h, representative of 3 independent experiments. Staining for the nucleus (blue) shows that Aβ1-42 peptides are internalized within the cells. Magnification = 63x, scale bar = 10 µm. Comparison of Aβ-uptake ability of M1- and M2- differentiated macrophages in FCS from patients with d AD vs. CO (n = 12, per group) and e APOEε4(+) and APOEε4(-) (n = 12, per group). f Genotype effect on the fold change in Aβ-uptake ability due to long-term compared to short-term M1-and M2- macrophage differentiation in FCS. Aβ-uptake levels in Mo-MФs were quantified with a bead-based immunoassay. Dots represent individual participant values (circle for AD and CO; square for APOEε4(+) and APOEε4(-)). Closed bars and symbols represent CO (light grey for short-term; dark grey for long-term) vs. AD (light red for short-term; dark red for long-term) and APOEε4(-) (light grey for short-term; dark grey for long-term) vs. APOEε4(+) (light green for short-term; dark green for long-term). Open bars and symbols represent APOEε4(-) (black), while open bars and closed symbols represent APOEε4(+) (green). The Friedman ANOVA was used to compare within-group differences, while the Mann Whitney U-test (paired groups) was used to assess between-group differences. Significant values of ANOVA tests were then subjected to Dunn's multiple comparison test with Bonferroni correction. Statistical significance was determined at the p ≤ 0.05 level unless a Bonferroni adjustment was required for multiple comparisons (p* < 0.0167 (p/n, assuming n = 3 comparison)