Figure 6

β-Arrestin1 deficiency reduces Aβ production and γ-secretase activity in APP/PS1 mice. (A) Reduced amyloid-β plaque in βarr1^−/− APP/PS1 mice was revealed by immunostaining with Aβ antibody 6E10 in coronal mouse brain ice sections (representative sections shown, measured by Image-Pro Plus 5.1, n = 4-5 for each group, P < 0.05). (B) Soluble and insoluble Aβ40 and Aβ42 in mice cortex (Cx) and hippocampus (Hp) were measured by Aβ40 or Aβ42 specific ELISA kit (upper and middle panel, n = 4-5 for each group, ^*P < 0.05, ^**P < 0.01). Aβ abundance was normalized to wet brain tissue weight. The Aβ42 to Aβ40 ratio remained unchanged upon β-arrestin1 knockout in APP/PS1 mice (lower panel, n.s., not significant). (C) Activities of α-, β-, and γ-secretase in hippocampal extracts of βarr1^+/+ APP/PS1 and βarr1^−/− APP/PS1 mice were determined by specific fluorogenic substrate assay (n = 4 for each group). ^***P < 0.001. (D) Western blot analysis of hippocampal protein extracts of βarr1^+/+, βarr1^+/+ APP/PS1 and βarr1^−/− APP/PS1 mice with the indicated antibodies. (E) Brain samples from βarr1^+/+ APP/PS1 and βarr1^−/− APP/PS1 mice were extracted under native conditions and subjected to BN-PAGE, analyzed by immunoblot using the indicated antibodies. β-Arrestin1 knockout reduces the amount of the mature γ-secretase complex. (F) Western blot analysis of β-arrestin1 in APP/PS1 mice hippocampal protein extracts. The APP/PS1 mouse aged from 7-8 months.