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. 2012 Dec 3;123(1):224–235. doi: 10.1172/JCI64516

Figure 7. AR-A014418 treatment significantly reduces neuritic plaque formation in AD transgenic mice.

Figure 7

(A and B) APP23/PS45 double transgenic mice at the age of 6 weeks were treated with ARA (5 mg/kg) for 4 weeks, while age-matched control APP23/PS45 mice received vehicle solution. The mice were sacrificed after behavioral tests, and the brains were dissected, fixed, and sectioned. Neuritic plaques were detected using Aβ specific monoclonal antibody 4G8 (Signet). The plaques were visualized by microscopy with ×40 magnification. (A) A representative brain section of the control and (B) AR-A014418 injected APP23/PS45 mice sacrificed immediately after behavioral analysis. Black arrows point to plaques. Bars: 500 μm. The number of neuritic plaques was significantly reduced in AR-A014418 treated mice compared to controls. (C) Quantification of neuritic plaques in APP23/PS45 mice with treatment starting at the age of 6 weeks and sacrificed immediately after behavioral analysis, the number represents mean ± SEM, n = 22 mice total, *P < 0.01 by Student’s t-test. (D and E) Neuritic plaques were further confirmed using thioflavin S fluorescent staining and visualized by microscopy with a ×40 objective. There were less neuritic plaques in AR-A014418 treated mice (E) as compared to age matched control mice (D) sacrificed immediately after AR-A014418 injection. White arrows point to green fluorescent neuritic plaques. Bar: 500 μm. (F and G) Plaque formation in APP23/PS45 mice was further examined using 4G8 antibody staining 3 months after the last injection. (F) A representative brain section of control or (G) AR-A014418 injected APP23/PS45 mice sacrificed 3 months after the last injection. (H) Quantification of neuritic plaques in APP23/PS45 mice 3 months after the last injection. The number represents mean ± SEM, n = 12 mice total, P > 0.05 by Student’s t-test.