Valsartan lowers brain β-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease
J. Clin. Invest. Jun Wang, et al. 117:3393 doi:10.1172/JCI31547 [
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Figure 4Valsartan treatments prevented cognitive impairment and attenuate AD-type neuropathology, in part, by promoting membrane-bound insulin degradation enzyme activity. (
A) APP content in the cortex of valsartan-treated or untreated control Tg2576 mice. Inset: Representative immunoreactive APP (C8 antibody) and β-actin signals. (
B) Assessments of cellular α-, β-, and γ-secretase activities in the cerebral cortex of Tg2576 mice in response to valsartan treatment. (
C) Assessment of Aβ
1–42 and Aβ
1–40 peptide content in peripheral blood (serum). (
D) Assessments of CM-associated (left panel) and cytosolic (right panel) IDE activity in the cerebral cortex of Tg2576 mice in response to valsartan treatment. Inset: Representative immunoblot signals of membrane and cytosolic IDE protein content from the same samples. (
E) Assessments of neprilysin content by Western blotting using a commercial rabbit anti-mouse neprilysin antibody. Inset: Representative neprilysin and actin protein signals from the same blot. (
F) Assessment of ECE activity using an Endothelin-1 ELISA System. Values represent group mean ± SEM;
n = 7–9 mice per group. *
P < 0.05; 1-way ANOVA, followed by Newman-Keuls post-hoc analysis.
