Cholesterol metabolism and brain amyloidosis: evidence for a role of copper in the clearance of Abeta through the liver.

Mounting evidence suggests that copper may influence the progression of Alzheimer's disease by reducing clearance of the amyloid beta protein (Ass) from the brain. We propose that Abeta is cleared from the brain by tagging along with cholesterol/ApoE in traversing the BBB, with subsequent incorporation into HDL for delivery of the toxin to the liver. It is suggested that either ABC-A1 or LRP, or both are involved in Abeta transport across the BBB, as well as normal cholesterol efflux. We have previously shown that addition of only 0.12 PPM copper (one-tenth the Environmental Protection Agency Human consumption limits) to distilled water was sufficient to precipitate the accumulation of Ass in the brains of cholesterol-fed rabbits. Here we show that in a setting of elevated cholesterol levels, overproduced Abeta is cleared to the blood and can simultaneously be identified in the liver if copper ion is absent from the animal's drinking water, but if trace levels copper (0.12 PPM) are added to the drinking water Abeta accumulates in the brain, while the levels in the liver are greatly reduced.