The Acyl-Coenzyme A:Cholesterol Acyltransferase Inhibitor CI-1011 Reverses Diffuse Brain Amyloid Pathology in Aged Amyloid Precursor Protein Transgenic Mice

摘要: Cerebral accumulation of amyloid-beta (Abeta) is characteristic Alzheimer disease and amyloid precursor protein (APP) transgenic mice. Here, we assessed the efficacy CI-1011, an inhibitor acyl-coenzyme A:cholesterol acyltransferase, which suitable for clinical use, in reducing pathology both young (6.5 months old) aged (16 human APP Treatment animals with CI-1011 decreased plaque load cortex hippocampus reduced levels insoluble Abeta40 Abeta42 C-terminal fragments brain extracts. In mice, specifically diffuse plaques a minor effect on thioflavin S-positive dense-core plaques. Reduced diffusible was accompanied by suppression astrogliosis enhanced microglial activation. Collectively, these data suggest that treatment reduces burden mice limiting generation increasing clearance Abeta.