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. 2021 May 25;12:3098. doi: 10.1038/s41467-021-23337-z

Fig. 1. Angiogenesis is concentrated around Aß plaques in AD mouse models.

Fig. 1

a Working model of the angiogenesis around Aß plaques. Aß deposition separate vessels (1) producing local hypoxia (2) and inducing angiogenic factors expression (3). b Coronal cortical sections of 14-month-old APP-PSEN1/+ mice treated with Hypoxiprobe (Pimonidazole HCl; 60 mg/kg i.p.; 45 min) showing hypoxia (brown, immunoperoxidase, DAB) in the vicinity of Aß plaques (green, Thioflavin-S staining –Thio-S–). The dashed square box is shown in the rightest panel. Scale bar = 100 and 25 µm, respectively, in low and high magnification images. c, d Vegfa is mainly expressed by astrocytes around Aß plaques in 8-month-old APP-PSEN1/+ mice. Aß plaques are indicated by a yellow asterisk. Cortical confocal XY images stained with astrocytic (GFAP; cyan; c), Vegfa (in situ hybridization, ISH; brown), Aß (Thio-S; green), microglial (IBA1; cyan, d), and nuclear (DAPI; blue) markers. White arrowheads indicate microglial cells without Vegfa expression and red arrowheads point to a non-microglial Vegfa-expressing cell (d). Scale bars (c, d) = 20 µm. e Quantification of the number of astrocytes (AS) and microglia (M) expressing Vegfa mRNA per Aß plaque. Mean ± SEM. n = 5 mice (5 Aß plaques per mice); Student’s t-test. f VEGF differentiates phalanx cells to tip cells that extrude from the vessel and stalk cells that will produce the new capillary (4). g A cortical mouse brain area stained with angiogenic endothelial (Integrin αvß3 –Iαvß3–; red), microglial (IBA1; green), endothelial (IB4; white), and nuclear (DAPI; blue) markers. Scale bar = 20 µm. Right graph, quantification of the Iαvß3+ cell density in 8-month-old wild-type (WT) and APP-PSEN1/+ mice. Mean ± SEM. n = 4 WT and 5 APP-PSEN1/+ mice; ANOVA, post hoc Tukey’s test.