Figure 5.
Acute and long-term treatment of Tg2576 mice with AZ-4217. Female Tg2576 (12 months at termination) mice were treated with 200 μmol/kg AZ-4217 acutely or repeatedly once daily for 7 and 28 d, terminated 4.5 h after last dose. Significant effects on brain hAβ40 and hAβ42 were only seen after 28 d of treatment in both the soluble (A, B) and the insoluble (C, D) brain pools. Target engagement was seen already after acute treatment both on brain sAPPβSWE, reduced, and brain sAPPα, elevated (E). The levels of sAPPβSWE (triangles) and sAPPα (squares) in DEA brain homogenates were stable in female Tg2576 mice between 3 and 24 months of age (F). Data are presented as mean values ± SEM (*p < 0.05; **p < 0.01, ***p < 0.001, compared with vehicle). The mean levels (pg/mg tissue ± SEM, n = 72/77) in the vehicle-treated groups were 396 ± 26 (soluble hAβ40), 207 ± 9 (soluble hAβ42), 2399 ± 193 (insoluble hAβ40), and 2961 ± 148 (insoluble hAβ42).