Cholesterol prevents Alzheimer's

Cholesterol prevents Alzheimer’s lood vessels work best when they are clear of cholesterol. But neurons need cholesterol to maintain top form, according to Abad-Rodriguez et al. (page 953). With too little of this membrane lipid, neurons produce more of the Alzheimer’sassociated amyloid peptide (A ). The results are a warning that the effects of cholesterol-lowering drugs may need to be confined to the liver, where circulating sterols and fatty acids are made. A production begins when the APP precursor protein is cleaved by the BACE1 -secretase. The new results show that cholesterol limits this cleavage by keeping BACE1 from its substrate. Most APP was found in cholesterol-free detergent-soluble domains, in which only 10% of the total APP was found in contact with BACE1. Much of the BACE1 was instead found in separate cholesterol-rich rafts. In cultured neurons treated with anti-cholesterol drugs, twice as much APP colocalized with BACE1, and the cells consequently secreted more A . Similarly, more BACE1 leaked into nonraft, lower cholesterol regions in neurons from Alzheimer’s patients. Clinical studies correlated the use of statins, which reduce primarily circulating cholesterol, with a lower, not higher, risk of Alzheimer’s. The authors suggest that this benefit may B