Fig. 4: OC+ clusters formation are exacerbated by presenilin 1 mutation in hAβ-KI mice. | Nature Communications

Fig. 4: OC+ clusters formation are exacerbated by presenilin 1 mutation in hAβ-KI mice.

From: Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer’s disease-like pathology

Fig. 4

a hAβ-KI mice (gray) are bred to homozygosity with PS1M146V mice (green) and aged to 18 months. b Aβ40 and Aβ42 levels in hAβ-KI (dark-gray) and hAβ-KI/PS1M146VKI (green) homozygous mice were quantified using the MSD V-PLEX Plus Aβ Peptide Panel 1 (6E10) Kit (n = 6 in hAβ-KI/PS1M146VKI group and n = 8 in hAβ-KI group). Soluble Aβ40 (b1, unpaired, two-tailed t-test, **p = 0.0041) and Aβ42 (b2, unpaired, two-tailed t-test, ****p < 0.0001) and insoluble Aβ40 (b3, unpaired, two-tailed, t-test ***p = 0.0009) and Aβ42 (b4, unpaired, two-tailed t-test, **p = 0.0013) showed an increase in hAβ-KI/PS1M146VKI compared to hAβ-KI mice. c Immunostaining for astrocytes (GFAP, red) and protofibrils (OC, green) shows accumulation of OC+ clusters in the hippocampus (high magnification images; c1b–c3b). AmyloGlo stain (blue channel) in hAβ-KI/PS1M146VKI homozygous mice (c4) shows that this line did not generate fibrillar aggregates. d–g Quantification of (c) showing the number of clusters per hippocampal slice (d) the average number of OC+ granules within an individual cluster (WT n = 6, hAβ-KI n = 18, hAβ-KI/PS1M146VKI n = 15; ANOVA, F2,45 = 13.11, Tukey’s post hoc test, **p < 0.01 and ***p < 0.001) (e) the average area of a single granule (WT n = 5, hAβ-KI n = 7, hAβ-KI/PS1M146VKI n = 10, One-way ANOVA, F2,19 = 0.1043, Tukey’s post hoc test, *p < 0.05), (f) and the average area taken up by a cluster (WT n = 5, hAβ-KI n = 7, hAβ-KI/PS1M146VKI n = 10, One-way ANOVA, F2,19 = 2.534, Tukey’s post hoc test, *p < 0.05), (g) in 18-month WT (blue), hAβ-KI (dark-gray) and hAβ-KI/PS1M146VKI (green) mice (WT n = 5, hAβ-KI n = 7, hAβ-KI/PS1M146VKI n = 10, One-way ANOVA, F2,19 = 0.1639, Tukey’s post hoc test, **p < 0.01). h–k Densitometric analysis using Imaris software to quantify density (h) and cell area (WT n = 6, hAβ-KI n = 7, hAβ-KI/PS1M146VKI n = 9) (i) of GFAP+ astrocytes or the density (j) and cell area (k) of IBA1+ microglia cells in 18-month WT (blue), hAβ-KI (dark-gray) and hAβ-KI/PS1M146VKI (green) mice (WT n = 7, hAβ-KI n = 7, hAβ-KI/PS1M146VKI n = 9, One-way ANOVA, F2,20 = 1.716, Tukey’s post hoc test, **p < 0.01 and F2,20 = 4.435, Tukey’s post hoc test, **p < 0.01). Data are presented as mean values ± SEM. Scale bar: 300 μm (c1–c3) and 100 μm (c4–c4b).

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