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Figure 7 | Alzheimer's Research & Therapy

Figure 7

From: Amyloid precursor protein selective gamma-secretase inhibitors for treatment of Alzheimer's disease

Figure 7

Reduction of Aβ and Math1 in FVB mice after treatment with ELN475516 or LY411575 for seven days. Female FVB mice were treated orally twice daily with ELN475516, LY411575 or vehicle and sacrificed at three hours post last dose. (a) Cortical Aβx-40 levels, estimated by ELISA from guanidine brain homogenates. Statistically significant (P <.0001) Aβ reduction (33%) was achieved at the lowest dose tested (15 mg/kg/dose). (b) Relationship of ELN475516 levels in plasma (estimated by LC/MS/MS) vs. brain Aβx-40 levels (estimated by ELISA from guanidine brain homogenates). Duodeneum (c) and Ileum (d) Math1 mRNA levels, estimated by TaqMan RT-PCR. Treatment with 5 mg/kg/dose LY411575 BID for seven days resulted in a robust elevation of Math1 gene expression in the duodeneum and ileum (P < 0.001). No effects on Math1 in the duodeneum or ileum were observed after treatment of ELN475516 BID for seven days up to the highest dose tested, 1,000 mg/kg/dose (2,000 mg/kg/day). Statistical significance between treatment groups and vehicle was determined by ANOVA and Dunnett's test. ***, P < 0.001

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