The 6E10 halo like surroundings of thioflavin S dense core plaques were significantly reduced. Using Iba 1, a marker for activated microglia, there was a substantial increase in the number of microglial cells per mm2 in the hippocampus. Microglial cell numbers inside the cortex were also increased but Ubiquitin conjugation inhibitor this didn’t achieve statistical significance. . Significantly, Iba 1 microglial cells appeared to be employed for the environments of big, DAPI, plaque like buildings in CI 1011 addressed minds. We performed a correlation analysis about the data, to find out if there is a relationship between plaque density and microglial activation. In CI 1011 treated animals there was a good correlation between thioflavin S dense core plaques and the amount of microglial cells that were more important and stronger than in the placebo treated group. A similar good correlation was found between the number of microglial cells and 6E10 diffuse plaque density in placebo treated mice, but in Metastasis CI 1011 treated mice the correlation was bad within both cortex and hippocampus. . These data suggest that CI 1011 can enhance glial responses in aged plaque bearing hAPP mice, and that microglia could have contributed to the settlement of diffuse amyloid deposits seen in CI 1011 treated animals. DISCUSSION Here we show that the clinically applicable ACAT inhibitor, CI 1011 decreases proteolytic processing of APP and AB generation in young mice and in old mice with pre-existing plaque pathology, it appears to lessen the diffuse amyloid stress, likely by decreasing generation of new AB. This results in partial reversal of amyloid pathology, suppression of astrogliosis and increased microglial activation. Treatment of young mice with CI 1011 corroborated our previous findings with an older generation ACAT chemical, CP 113,818. CI 1011 ATP-competitive Chk inhibitor seems to be slightly less effective than CP 113,818 with regard to effects on brain cholesteryl ester, amyloid plaque load and AB levels,, which is consistent with its lower antagonistic potency on ACAT. . Significantly, in both studies all critical parameters seem to correlate closely with brain cholesteryl ester levels. Statins, common inhibitors of cholesterol biosynthesis, lower total cholesterol in cells and lead to paid down AB production in many cell and animal models of AD. Generally in most animal studies employing statins and other inhibitors of the cholesterol biosynthetic pathway, drug administration was started before plaque deposit begins, making comparison of CI 1011 therapy to statins complex. Apparently, one survey showed that lovastatin treatment of 12-month old Tg2576 rats for 3 months didn’t affect amyloid load or brain AB levels in males although it increased AB pathology in female animals.