| In Vivo |
CP-113818 (0-7.1 mg/kg/day) markedly reduces amyloid pathology in a mouse model of Alzheimer's disease[1]. Animal Model: C57BL/6, hAPP (human amyloid precursor protein) transgenic mice[1] Dosage: 0, 0.2, 1.6, 3.2, 4.8, and 7.1 mg/kg/day Administration: Via implantable slow-release biopolymer pellets, 21 days for nontransgenic mice or 60 days for hAPP mice Result: Reduced total cholesterol levels by 29% in the serum, hepatic free cholesterol and cholesteryl-esters were also decreased in a dose-dependent manner by up to 37% and 93%, respectively in the nontransgenic mice. Effectively reduced cholesteryl-ester levels of hAPP mice in the absence of adrenal toxicity, reduced plaque numbers, and decreased amyloid load in a gender-independent manner in hAPP mice. Reduced levels of “insoluble” and soluble Aβ1-40 and Aβ1-42 in the brains of hAPP transgenic mice. Restored normal spatial learning and memory in female hAPP mice in a morris water maze test. Reduced processing of endogenous APP but not notch or N-cadherin, without directly inhibiting β- and γ-secretase activities or Aβ aggregation in nontransgenic littermates.
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