Fig. 8: Astrocyte-specific inactivation of Sorcs2 increases Aβ levels and induces cell stress in the PDAPP mouse brain. | Nature Communications

Fig. 8: Astrocyte-specific inactivation of Sorcs2 increases Aβ levels and induces cell stress in the PDAPP mouse brain.

From: Astrocytes distress triggers brain pathology through induction of δ secretase in a murine model of Alzheimer’s disease

Fig. 8

a Levels of soluble Aβ40 and Aβ42 in hippocampus (hip) and cortex (cx) of 32 weeks old PDAPP animals (20 weeks post tamoxifen injection) homozygous for Sorcs2lox/lox (PDAPP/loxWT) or carrying an astrocyte-specific Sorcs2 gene defect (PDAPP/asKO). Data are given as mean ± SEM from n = 8 (Aβ40, asKO), n = 9 (all other groups) animals per group (two-sided unpaired Student’s t-test). b Data as in (a), but from hip and cx extracts of 38 weeks old PDAPP/loxWT and PDAPP/asKO animals. Data are given as mean ± SEM for n = 9 (loxWT), n = 11 (hip, Aβ40, asKO) n = 12 (other groups) animals per group (two-sided unpaired Student’s t-test). c Levels of soluble Aβ40 and Aβ42 in cx and hip of 38 weeks old male mice, either PDAPP/loxWT or carrying a neuron-specific Sorcs2 gene defect (PDAPP/nsKO). Data are given as mean ± SEM for n = 13 (Aβ40 and Aβ42, hip nsKO), n = 12 (other groups) animals per group (two-sided unpaired Mann-Whitney U test). Representative Western blot for GFAP and IBA1 in hip (d, upper panel) or cx brain extracts (d, lower panel), and quantification from densitometric scanning of replicate blots thereof (e), are shown. Data are expressed as relative to WT (set to 100%) and given as mean ± SEM from n = 6 animals per genotype (two-sided unpaired Mann-Whitney U test). f Nucleosome fragmentation assay documenting cell death in hip extracts of 38 weeks old PDAPP/asKO females and matched PDAPP/WT. Data are given as mean ± SEM from n = 9 (loxWT), n = 12 (asKO) animals per group (two-sided unpaired Mann-Whitney U test). Levels of IL-33 in hip (g) and cx (h) extracts of PDAPP/WT or PDAPP/KO female mice at 38 weeks of age. Young females are separated into two groups based on low versus high brain Aβ levels (cut off: 300 pg/ml Aβ40 and 800 pg/ml Aβ42 for hip; 35 pg/ml Aβ40 and 60 pg/ml Aβ42 for cx). Data are given as mean ± SEM from n = 8 (g, 20 w.), n = 9 (g, 38 w. loxWT), n = 10 (h, 38 w. loxWT), n = 11 (h, 38 w. asKO; h, 20 w. KO low), n = 12 (h, 38 w. asKO), n = 13 (h, 20 w. KO high), n = 14 (h, 20 w. WT) animals per group (two-sided unpaired Student’s t-test). p-values for all statistically significant differences are indicated on the graphs. Source data are provided in the Source Data file.

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