Inhibition of ACAT function in cells either by genetic or pharmacological means is demonstrated to effortlessly reduce A technology. Metaanalysis of genetic information suggests that SOAT1 is linked to the risk of AD and that a standard polymorphism that results in lowered Erlotinib ic50 ACAT action might confer protection against AD. Several ACAT inhibitors have been developed by the pharmaceutical industry for treatment of atherosclerosis and hyperlipidemia which are safe for human use and can be utilized to review the role of ACAT in AD. We have previously shown that the 2 month treatment with CP 113818 remarkably reduced amyloid pathology and correlated with improved spatial learning in transgenic mice expressing human APP 751 containing the London and Swedish mutations. Avasimibe is a widely studied ACAT inhibitor that’s structurally unrelated to CP 113818. The pharmacological profile of avasimibe is somewhat distinctive from CP 113818. For example, IC 50 values for avasimibe and CP 113818 are 391 and 6 n M for HepG2 cells, and 664 and 63 n M for THP 1 cells, respectively. Though IC 50 values are lower for CP 113818, the ACAT1/ACAT2 selectivity is slightly greater for avasimibe. As a proof of principle experiment, we have addressed two Cellular differentiation age brackets of nontransgenic mice and female hAPP FAD with two different doses of avasimibe. Avasimibe was applied in the form of implantable biopolymer pellets for just two months. Serum cholesterol levels suggested that avasimibe therapy was significantly less effective in inhibiting ACAT when compared with CP 113818, while neuropathological and bio-chemical studies of brain amyloid plaque weight are still continuing. This effect was expected, taking into consideration the approximately 10-fold higher IC 50 value of avasimibe in comparison with CP 113818. As yet another evidence of concept design for ACAT task regulating A technology, we’ve applied ACAT1 RNAi in individual H4 neuroglioma cells. Lowering ACAT1 protein levels by about 50-cycle resulted in significant decreases in APP mapk inhibitor CTF levels in cell lysates in addition to secreted An in the conditioned media. Altogether, we’ve successfully used a few independent pharmacological and genetic methods to reduce ACAT activity in cell based and animal models, that have proved to effectively attenuate A generation and amyloid pathology. An important distinction between ACAT inhibitors and statins could be the process whereby they attenuate An era. Inhibition of HMG-COA reductase by statins shuts down the L mevalonate pathway affecting many cholesterol and isoprenoid dependent processes inside the cell. Cholesterol-rich membrane domains such as lipid rafts that are enriched in secretase and both activities are strongly affected by statin treatment. We’ve used 2 dimensional LC MS to recognize proteins that bind to APP differentially in ACAT inhibitor treated cells. A few ER proteins, including chaperones of the GRP family, were defined as ACAT chemical open APP interacting proteins.