Figure 4.

Microglia process dynamics and length are altered in relation to amyloid. A, Two time points, separated by 9 min, are superimposed with voxels that were present in the first but not the second (retraction) indicated in purple, and in the second but not the first (extension) indicated in yellow, with all unchanged voxels in white. Process retractions and extensions in microglia from APPPS1⁻ mice typically occur isotropically distributed throughout their ramified tree structure. In APPPS1⁺ mice, polarized microglia (arrow) and macrophagic microglia (arrowhead) “near” or “on” amyloid plaques no longer survey their environment in a distributed, isotropic manner. Inset, Right panel, Process movement (in this case, extension) was measured with lines drawn in three dimensions between the start and end of new processes. Scale bar, 50 μm. B, Significant differences in the total process length per cell were seen for the different categories, with microglia near plaques exhibiting increased process length, and those immediately “on” plaques with substantially reduced length (main group effect, F _(1,22) = 22.2; p < 0.01 for all comparisons). Both types of plaque-associated microglia also showed significant polarity (indicated for the “near” microglia by diagonal shading for processes oriented toward plaques and solid for processes oriented in the opposite direction), with microglia “on” plaques only having processes oriented away from the plaque surface. C, Although morphology between the microglia types was substantially altered, the overall extent of process movement was similar (analyzed microglia: APPPS1⁻, n = 10; APPPS1⁺“near”, n = 10; APPPS1⁺“on”, n = 6), with only the microglia “on” amyloid exhibiting a slight but significant change in speed of process extension/retraction (μm/time point − 9 min).