Fig. 8

Apoe protein is present within and compartmentalized with Aβ within plaque-associated microglia in 5xFAD mouse brain. a Comparison of Apoe transcript and protein expression in CNS cells (astrocytes, microglia, neurons and oligodendrocytes). Data were derived from existing brain cell-type specific RNA sequencing and proteomics datasets [8, 29]. b Immunofluorescence micrographs (maximal projections of Z-stack confocal microscopic images) showing Aβ (4G8, Blue), Iba1 (Green) and Apoe (Red) expression in 5xFAD mouse brain. Overlap between Iba1 and Aβ (White) and between Iba1 and Apoe (White) are shown in two-channel merged images. c 3D reconstructions of 0.5 μm thick confocal microscopic Z-stack images from 5xFAD mouse brains showing intra-microglial Aβ (Yellow) and intra-microglial Apoe (White). Co-localization between intra-microglial Aβ and Apoe is shown in light pink (right). Degree of co-localization (correlation) between Apoe-positive and Aβ-positive pixels is shown in the inset image (R² = 0.88). d Comparison of intra-microglial Apoe in ramified microglia (wild-type mice) with Aβ plaque-associated microglia (5xFAD mice). Proportion of Apoe+ pixels within Iba1+ microglia (ramified or plaque-associated) was determined by co-localization analysis as shown in panels (b) and (c). N=5 images (subiculum of the hippocampal formation) from 3 WT and 3 5xFAD mice were obtained (*** p < 0.005)