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Jun Wang, Lap Ho, Linghong Chen, Zhong Zhao, Wei Zhao, Xianjuan Qian, Nelson Humala, Ilana Seror, Sadie Bartholomew, Clive Rosendorff, Giulio Maria Pasinetti
Published in Volume 117, Issue 11
J Clin Invest. 2007; 117(11):3393–3402 doi:10.1172/JCI31547
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Figure 3
Chronic valsartan treatment of Tg2576 mice resulted in dose-dependent attenuations of AD-type spatial memory deterioration in Tg2576 mice, which is coincidental with significant reductions in HMW soluble Aβ species and AD-type neuropathology in the brains of Tg2576 mice.

(A) The influence of Aβ-related spatial memory in response to valsartan treatment at 10 and 40 mg/kg/d versus the untreated control Tg2576 mice was assessed using an MWM test in approximately 11-month-old female Tg2576 mice. Latency score represents time taken to escape to the platform from the water. (B) Assessments of soluble, extracellular HMW Aβ peptide contents in the brain using an antibody specific for HMW oligomeric Aβ peptides in a dot blot analysis. Inset: Representative dot blot analysis of HMW soluble Aβ contents. (C) Assessment of total PBS-soluble Aβ peptide using ELISA assay. (D) Assessment of Aβ1–42 and Aβ1–40 peptide concentrations in the cerebral cortex and hippocampus of valsartan-treated (10 or 40 mg/kg/d) or control mice. (E) Stereological assessment of cerebral cortex and hippocampal Aβ plaque burden in valsartan-treated or control mice expressed as thioflavin-S–positive volume as a percentage of regional volume. Inset: Representative photograph of thioflavin-S–positive Aβ plaque neuropathology in neocortex (CTX) and hippocampal formation (H) in untreated control (left panel) and valsartan-treated (40 mg/kg/d) Tg2576 mice (right panel). Arrowheads point toward thioflavin-S positive amyloid plaques. Original magnification, ×125. Values represent group mean ± SEM; n = 7–9 mice per group. In B and C, *P < 0.001; In D and E, *P < 0.05, **P < 0.01; 1-way ANOVA followed by Newman-Keuls post-hoc analysis.