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

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

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*

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.
*Diarrhea and hair loss.

ISSN: 1750-1326