Extended Data Fig. 12: LD accumulation impairs iMG phagocytosis.

(a) Representative fluorescence images show time-dependent phagocytosis of Aβ-pHrodo and LD accumulation (BODIPY+) in iMG (CD45+) carrying the LOAD risk-allele or non-risk allele of PICALM in the presence or absence of TrC. Scale bar, 100 μm. (b) Reduced Aβ-pHrodo intensity in iMG carrying the LOAD risk-allele (vs. non-risk) can be rescued by TrC treatment. (c) TrC treatment rescues the LD in iMG carrying the LOAD risk-allele to a level similar to that in MG with the non-risk allele. (d) Pie charts show the proportion of iMG (CD45+) stained positive for Aβ-pHrodo, BODIPY, or both from co-localization analysis of the fluorescence images in (a). Note that TrC treatment rescues the phagocytosis deficit in iMG carrying the LOAD risk-allele by mainly converting BODIPY+ iMG to phagocytic cells without LD (Aβ-pHrodo+/BODIPY-). (e) to (h) The same as in (a) to (d) except that the phagocytosis assay was for myelin-pHrodo. In (a) to (h), each datapoint represents a single-well measurement (FOV) from one experiment; for each condition (risk, risk-TrC, and non-risk), data are from CD09 line (one clone), collected from one experiment with 2-3 differentiations each with 2–4 FOV. One-way ANOVA with Dunnett’s correction; * P < 0.05, ** P < 0.01, ***, P < 0.001; mean ± s.e.m.