Extended Data Fig. 11: iMG carrying the LOAD risk-allele of rs10792832 show increased lipid peroxidation.

(a) The schematics show C11-BODIPY (581/591), a fluorescent lipid peroxidation sensor, shifts its fluorescence from red to green in the presence of ROS. Illustrations were created using BioRender. Sudwarts, A. (2025) https://BioRender.com/21bufax. (b) Fluorescence staining with peroxidation sensor C11-BODIPY in iMG (TREM2⁺) carrying the LOAD risk or non-risk allele in the presence or absence of TrC. Scale bar, 50 µm. (c) and (d) Increased LD (C11-BODIPY green fluorescence) density and area in iMG carrying the LOAD risk-allele (vs. non-risk). Note the peroxidized LD density and area are reduced in iMG treated with TrC. (e) The ratio of peroxidized vs. non-peroxidized (BD.11 Ox/BD.11 non−ox) lipids in iMG carrying the LOAD risk-allele or non-risk allele, with or without TrC treatment. Each datapoint represents a single-well measurement (FOV) of one experiment; for each condition (risk, risk-TrC, non-risk, and non-risk-TrC), data are from line CD04 (one clone), collected from one experiment with 3 wells of differentiations each with 2-3 FOV. For all comparisons, one-way ANOVA with Tukey’s correction; * P < 0.05, ** P < 0.01, ***, P < 0.001; mean ± s.e.m. (f) Mechanistic insight on the link between the LOAD GWAS SNP risk allele and the reduced PICALM expression, lysosomal dysfunction, LD accumulation, LD peroxidation, cellular ROX level, and phagocytosis deficits in iMG. (-), inhibition; FA: fatty acids; Px: peroxisome; M: mitochondria; sER: smooth ER; Ly: lysosome; Chl: cholesterol. Illustrations were created using BioRender. Sudwarts, A. (2025) https://BioRender.com/bmv8afh.