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.
References
[1] Hutter-Paier B, et al. The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer's disease. Neuron. 2004 Oct 14;44(2):227-38. DOI:10.1016/j.neuron.2004.08.043
