Figure 5
From: High Resolution Dissection of Reactive Glial Nets in Alzheimer’s Disease
Mouse RGNs in the CRND8 AD model share features with human RGNs and associate with neuronal pathology and Tau granules.
(a) Time-course for the assembly of RGNs around Aβ deposits. At 2 months, low numbers of activated microglia and reactive astrocytes surround small Aβ deposits. At 4 months, well-constructed RGNs are found. By 12 months, organization of the RGN is degraded and amoeboid microglia and reactive astrocytes can be located distal to RGNs surrounding Aβ deposits. (b) 3D analysis of astrocyte and microglia position around Aβ deposits at mid-stages of the disease in the CRND8 model (3–5 months). (c) Graph showing the positive correlation between astrocyte and microglial cell number and Aβ deposit volume at mid-stages of the disease (r = 0.264 for total Iba1+ cells, r = 0.488 for Iba1+ cells within GFAP shell and r = 0.561 for GFAP+ cells; pooled data, 3 to 5 month old mice). (d) Comparisons between plaques at mid- (3–5 months) and late-stages (8–9 months) of interval of inter-distance of GFAP+ cells from plaques (F(1, 57) = 14.635; p = 0.0003), numbers of Iba1+ cells within the astrocyte shell of the RGN (F(1, 57) = 7.725; p = 0.0074) and volume of the plaques (F(1, 57) = 5.425; p = 0.0234]. *p < 0.05, **p < 0.01 and ***p < 0.001). (e–g) Abnormal neuronal processes (e; SMI 312+; magenta) and granules of hyperphosphorylated Tau (f,g); detected by two different phospho-Tau antibodies PS422 (magenta) and AT8 (green), associated with RGNs. (h) Expression of IL-6 (upper panel, magenta) and IL-1β (lower panel, magenta) by GFAP+ astrocytes (green, arrows) in CRND8 mice at 9 months. (i) Western blot analysis of overall increases in IL-6 and IL-1β expression (mature form at 17 kDa, arrowhead) in the cortex of transgenic mice at 1, 4 and 9 months (with n = 3 for control and Tg+ at 1 month, n = 4 for control and n = 3 for Tg+ at 4 months and n=4 for control and n = 4 for Tg+ at 9 months). (j) IL-1β clusters (green) are closely juxtaposed to hyperphosphorylated Tau granules (AT8; magenta) in CRND8 mice. Scale bars: 20 μm (a,e–h), 5 μm (j).
