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Table 1 Brain and plasma Aβ40 levels following in vivo GSI treatment in Tg2576 mice

From: Transient pharmacologic lowering of Aβ production prior to deposition results in sustained reduction of amyloid plaque pathology

Compound Strain of Mice Route Dose Length of Treatment % Aβ40 ReductionBrain % Aβ40 ReductionPlasma Overt Toxicity
LY-411, 575 Tg2576 Intraperitoneal 5 mg/kg 6 hrs 75% 92% No
10 mg/kg 6 hrs 77% 96% No
25 mg/kg 6 hrs 78% 92% No
LY-411, 575 Tg2576 Oral (Suspension in Kool-Aid) 10 mg/kg/day 1 Day 47% 70% No
3 Days 65% 86% No
7 days 75% 95% No
LY-411, 575 Tg2576 Oral (Formulated In Rodent Chow) 1 mg/kg/day 2 weeks 36% 67% No
2.5 mg/kg/day 2 weeks 51% 78% No
5 mg/kg/day 2 weeks 78% 91% Yes*
10 mg/kg/day 2 weeks 83% 95% Yes*
  1. Tg2576 mice (3 months old) were dosed with GSI LY-411,575 using various routes, time points and indicated doses. After GSI treatment, groups of mice (n =3/group) were sacrificed and mouse brains were harvested and extracted in 2% SDS. Brain and plasma Aβ40 levels were then measured by ELISA.
  2. *Diarrhea and hair loss.