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. 2010 May 12;30(19):6743–6750. doi: 10.1523/JNEUROSCI.1381-10.2010

Figure 4.

Figure 4.

Plasma levels of Aβ during and after γ-secretase inhibition indicate peripheral Aβ rebound in rhesus monkeys treated with a CNS-penetrant GSI. A, Concentration of GSI in rhesus monkey plasma after dosing with GSI. B, Aβ levels in rhesus monkeys (n = 6), measured by ELISA are shown normalized to baseline. A dose–response effect on Aβ levels was observed with 60 mg/kg and 240 mg/kg. Plasma Aβ levels in the 60 mg/kg dose group recovered to baseline after 24 h, and then increased above baseline. Means between vehicle and 60 mg/kg from hours 33–48 are significantly different (paired t test, ***p < 0.0001). C, D, In an extended study (n = 6, 3/group), animals were treated with either vehicle or 240 mg/kg GSI. C, Concentration of GSI in rhesus monkey plasma after dosing with 240 mg/kg GSI. D, Plasma Aβ levels overshoot baseline after 48 h in 240 mg/kg GSI-treated animals (unpaired t test, ***p < 0.0001, h48–240). (vehicle, black circle; 60 mg/kg, blue square; 240 mg/kg, red triangle). Error bars indicate SEM.