Fig. 5: Phenotypic alterations in CNS of hAβ-KI mice. | Nature Communications

Fig. 5: Phenotypic alterations in CNS of hAβ-KI mice.

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

Fig. 5: Phenotypic alterations in CNS of hAβ-KI mice.The alternative text for this image may have been generated using AI.

a hAβ-KI (green) mice showed cortical deficits at 14, 18 and 22 months compared to WT (blue mice) (unpaired, two-tailed t-test, 14 mo *p = 0.0381, 18 mo *p = 0.0131 and 22 mo **p = 0.0024) (WT 2 mo n = 11, 6 mo n = 13, 10 mo and 14 mo n = 16, 18 mo n = 12, and 22 mo n = 20; hAβ-KI 2 mo, 18 mo and 22 mo n = 18, 6 mo n = 16, 10 mo n = 13 and 14 mo n = 14). b Hippocampal deficits were also observed in hAβ-KI (green) mice at 10, 14, 18 and 22 months compared to WT (blue) mice (unpaired, two-tailed t-test, 10 mo **p = 0.0037, 14 mo *p = 0.0239, 18 mo *p = 0.0112 and 22 mo **p = 0.0020) (WT 2 mo n = 15, 6 mo n = 14, 10 mo n = 18, 14 mo n = 20, 18 mo n = 12, 22 mo n = 19; hAβ-KI 2 mo and 22 mo n = 18, 6 mo and 18 mo n = 15, 10 mo n = 13 and 14 mo n = 14). c Acute hippocampal slices were examined for changes in synaptic plasticity in 2 and 18-month-old WT (gray = 2 mo and white = 18 mo) and hAβ-KI (blue = 2 mo and green = 18 mo) mice. Theta burst induced LTP was impaired in slices from hAβ-KI mice (2 mo and 18 mo n = 13 slices) relative to aged-matched WT controls (2 mo n = 14 slices, 18 mo n = 20 slices). Synaptic responses in control pathway remained stable (no theta stimulation) throughout the recording session. Insets show field synaptic responses collected during baseline (black line) and 1 h after theta burst stimulation (red line). Scale: 1 mV/5 ms. Mean (±SEM) percent potentiation 50–60 min post-TBS was markedly depressed in slices from hAβ-KI mice relative to WT controls (two-way ANOVA, major effect in interaction F1,56 = 22.46 and age factor F1,56 = 64.52, Tukey’s post hoc test, **p < 0.01 and ****p < 0.0001). d, e Confocal images of synaptic puncta stained with synaptophysin (green) and PSD-95 (red) antibodies, shows a significant decrease at presynaptic level in hAβ-KI (d4–d6; green) versus WT (d1–d3; blue) mice at 18 months (unpaired, two-tailed t-test, **p = 0.0062) (n = 5/genotype). f Cavalieri method shows significant differences in hippocampal volume between WT (blue) and hAβ-KI (green) mice at 22 months of age (unpaired, two-tailed t-test, *p = 0.0199; n = 4 in 6 mo-WT and 2 mo-hAβ-KI, n = 5 in 2 mo-WT, 10 mo-WT and 6 mo-hAβ-KI, n = 6 in 14 mo, 18 mo, 22 mo-WT and 10 mo, 14 mo, 18 mo and 22 mo-hAβ-KI). Data are presented as mean values ± SEM. Scale bar: 10 μm (d1–d6).

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